Abstract

A compound of formula I, or a salt, solvate or prodrug thereof: Q-L-M (I) wherein Q is a protein binding moiety of formula Q1 or Q2, L is a linker moiety; and M is an E3 ubiquitin ligase binding moiety. Also, a pharmaceutical compositions and combinations comprising compounds of formula I and the use of said compounds, compositions and combinations in therapy, particularly in the treatment or prevention of diseases or conditions mediated by RIPK1 kinase.

IPC Classes  ?

• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 471/04 - Ortho-condensed systems
• C07D 471/10 - Spiro-condensed systems
• C07D 498/04 - Ortho-condensed systems
• C07D 513/04 - Ortho-condensed systems
• A61K 31/428 - Thiazoles condensed with carbocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to a method for predicting whether a subject having cancer will benefit from G quadruplex binding ligand treatment by determining the level of one or more subunits of the SWI/SNF complex in a biological sample. The present invention also relates to the use of a G quadruplex binding ligand in inducing cell death of cancer cells deficient in a subunit of the SWI/SNF complex. The methods, compositions and uses described herein may be used to induce cell death of cancer cells deficient in a subunit of the SWI/SNF complex. The cells may be in vitro, ex vivo or in vivo. The cancer cells deficient in a subunit of the SWI/SNF complex may be present within a subject (e.g. cancer patients carrying a SWI/SNF subunit deficient malignant tumour).

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X1, X2, R1, R2 and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 471/04 - Ortho-condensed systems
• C07D 471/08 - Bridged systems
• C07D 487/04 - Ortho-condensed systems

Abstract

The disclosure is in part directed to a method of treating a cancer in a patient in need thereof, comprising administering to the patient an effective amount of a HSF1 pathway inhibitor, wherein the cancer comprises solid tumors identified as having an ARID1A mutation.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to methods for preparing complementary deoxyribonucleic acid (cDNA) molecules comprising T cell receptor (TCR) sequences and determining the nucleic acid sequence of those TCRs.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay

Abstract

The present invention relates to adenosine deaminase 1 (ADAR1) inhibitors for use in a method of treating an individual with a homologous recombination defective (HRD) cancer, as well as methods for selecting individuals suitable for such treatments.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.

IPC Classes  ?

• A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/4706 - 4-Aminoquinolines8-Aminoquinolines, e.g. chloroquine, primaquine
• A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate

Abstract

Methods and systems for analysing the cellular composition of a sample are described, comprising: providing an image of the sample in which a plurality of cellular populations are associated with respective signals and classifying a plurality of query cells in the image between a plurality of classes corresponding to respective cellular populations in the plurality of cellular populations. This is performed by providing a query single cell image to an encoder module of a machine learning model to produce a feature vector for the query image, and assigning the query cell to one of the plurality of classes based on the feature vector for the query image and feature vectors produced by the encoder module for each of a plurality of reference single cell images. The machine leaning model comprises: the encoder module, configured to take as input a single cell image and to produce as output a feature vector the single cell image, and a similarity module configured to take as input a pair of feature vectors for a pair of single cell images and to produce as output a score indicative of the similarity between the single cell images. Thus, the machine learning model can be obtained without the need for an extensively annotated dataset. The methods find use in the analysis of multiplex immunohistochemistry/immunofluorescence in a variety of clinical contexts.

IPC Classes  ?

• G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
• G06V 10/74 - Image or video pattern matchingProximity measures in feature spaces
• G06V 10/772 - Determining representative reference patterns, e.g. averaging or distorting patternsGenerating dictionaries
• G06V 10/774 - Generating sets of training patternsBootstrap methods, e.g. bagging or boosting
• G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks

Abstract

The present invention relates to compounds that function as inhibitors of BCL6 (B-cell lymphoma 6) activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

The present invention provides novel drug-inducible degradation tags (degrons), as well as fusion proteins, cells and pharmaceutical compositions comprising the same. Nucleic acid sequences and vectors encoding the novel degrons are also provided. Methods of using the novel degrons, fusion proteins, cells, pharmaceutical compositions, nucleic acid sequences and vectors are also provided herein.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/62 - DNA sequences coding for fusion proteins
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

Abstract

The invention relates to methods for treating prostate cancer by targeting the generation of splice variants of the androgen receptor. In one aspect, this can be achieved by targeting JMJD6 to reduce the production of androgen receptor splice variants. The invention finds particular use in the treatment of prostate cancer that is resistant to conventional androgen therapy.

IPC Classes  ?

• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

Methods and systems for determining the direction of a travelling shear wave within tissue. To determine the direction of a travelling shear wave within tissue, a travelling shear wave is generated within tissue using a vibrational source vibrating at a frequency; the tissue is imaged using a medical imaging modality to obtain images of the tissue; the images of the tissue are processed to obtain a 2D or 3D amplitude and/or phase representation of the travelling shear wave; a spatial shear wave autocorrelation function is calculated in dependence on the 2D or 3D amplitude and/or phase representation; and the direction of the travelling shear wave is determined using the autocorrelation function. Methods and systems for analysing the quality of a detected shear wave within tissue and acquiring image data of a steady state shear wave field within tissue are also provided.

IPC Classes  ?

• A61B 8/08 - Clinical applications

Abstract

Described herein are compounds of formula I, or a salt or solvate, thereof formula (I). Also described are pharmaceutical compositions and combinations comprising the compounds, and their use in the treatment of conditions mediated by lysyl oxidase, for example proliferative diseases, such as cancer and fibrotic disorders.

IPC Classes  ?

• C07D 333/34 - Sulfur atoms
• C07D 277/36 - Sulfur atoms
• A61P 35/00 - Antineoplastic agents
• A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
• A61K 31/426 - 1,3-Thiazoles

Abstract

Provided is a compound, or a salt or solvate thereof, according to formula I: as defined herein, and pharmaceutical compositions and combinations comprising said compounds. Also described are said compounds for use in therapy, in particular for use in methods of treating or preventing proliferative disorders, such as cancer, and fibrotic disorders.

IPC Classes  ?

• C07D 277/36 - Sulfur atoms
• A61P 35/00 - Antineoplastic agents
• A61K 31/426 - 1,3-Thiazoles

Abstract

The present invention provides a method of stratifying an individual suffering from a cancer for treatment with a compound for inhibiting monopolar spindle 1 (Mps1) and a compound for inhibiting Mps1 for use in a method of treating a PBRM1-defective cancer in an individual in need thereof. A kit comprising a reagent for detecting deficient PBRM1 in a sample from a subject and a compound for inhibiting Mps1 and a signature biomarker panel characteristic of response to treatment of a cancer with a compound for inhibiting Mps1 are also provided.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61P 35/00 - Antineoplastic agents
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

A method of predicting a patient's prognosis of prostate cancer, the method comprising providing and analysing a patients germline genetic material and detecting germline variants of genes up-regulated by activation of the PI3K/AKT/mTOR pathway, genes up-regulated by activation of the PI3K/AKT/mTOR pathway, genes up-regulated by KRAS activation, genes up-regulated in response to low oxygen levels, genes regulated by NF-kB in response to tumour necrosis factor (TNF) and/or genes specifically up-regulated in pancreatic beta cells or at least one gene from Table 1. Also provided is a method of determining treatment regimen and a biomarker panel.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention provides a method for predicting the treatment response of a human bladder cancer patient, the method comprising: a) measuring the gene expression of at least 9, at least 10, at least 15, at least 20 or at least 30 of the genes from Group 1 in Table 10 and at least 1, at least 2, at least 3 or at least 5 of the genes from Groups 2-4 in Table 10 in a sample obtained from the bladder tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Related methods and systems are also described. The invention finds particular use in predicting whether a bladder cancer patient is likely to be sensitive to (chemo)radiation therapy.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

A computer-implemented method is provided for delineating one or more parts of a body within a diffusion weighted MRI 3D patient image of a human or animal body. The method includes: providing the diffusion weighted MRI 3D patient image of the human or animal body, the patient image being formed of plural slices stacked along a direction of the body; analysing the patient image to identify different contiguous anatomical regions of the body, the regions being distributed along said direction such that each slice of the patient image is allocated to a respective region; providing an atlas of diffusion weighted MRI 3D ground truth images of plural other corresponding bodies containing the regions, each ground truth image being formed of plural slices stacked along a corresponding direction of the respective body, the different regions of the body being pre-identified for each ground truth image such that each slice of that ground truth image is allocated to a respective region, and one or more parts of the body of each ground truth image being pre-delineated; registering each ground truth image to the patient image by: translating and stretching each ground truth image in its corresponding direction to align the identified regions of that ground truth image with the corresponding identified regions of the patient image; identifying a transformation of each registered ground truth image that matches the pre-delineated parts of the body of that registered ground truth image to the corresponding parts of the body of the patient image by minimising a cost function; and segmenting the patient image by obtaining a probability image for the corresponding parts of the body of the patient image, wherein the probability image combines the pre-delineated parts of the bodies of the ground truth images transformed according to their respective non-linear deformable transformations and weighted according to their respective cost-functions.

IPC Classes  ?

• G06T 7/00 - Image analysis
• G06T 7/174 - SegmentationEdge detection involving the use of two or more images
• G06T 7/11 - Region-based segmentation

Abstract

An agent that generates DNA replication stress and/or inhibits pathways involved in DNA replication stress tolerance for use in a method of treating a patient with cancer. The treatment comprises: determining whether the cancer expresses HORMAD1; and, if so, administering to said patient an agent that generates DNA replication stress and/or inhibits pathways involved in DNA replication stress tolerance.

IPC Classes  ?

• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep

Abstract

The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X1, X2, R1, R2, R30, R31 and Ring A are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• A61P 35/00 - Antineoplastic agents
• C07D 471/04 - Ortho-condensed systems
• C07D 498/14 - Ortho-condensed systems
• C07D 498/20 - Spiro-condensed systems
• C07D 513/04 - Ortho-condensed systems
• C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and/or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and/or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 15/90 - Stable introduction of foreign DNA into chromosome
• C12N 15/86 - Viral vectors
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61P 35/00 - Antineoplastic agents

Abstract

A method of analysing magnetic resonance images of an object is provided. The method includes steps of: receiving an ADC (apparent diffusion coefficient) map of an object acquired by the performance of MRI (magnetic resonance imaging) of the object at respective and different b-values or receiving data from which the ADC map is derivable, the ADC map mapping values of ADC at respective positions across the object, the ADC value at a respective position being the negative gradient from a fitting to data points on a graph of the log of the intensities of the MRI signals acquired at that position against the b-values used to obtain the MRI signals; and using a neural network to calculate a predicted uncertainty map of the ADC values of the ADC map, the predicted uncertainty map mapping values of predicted uncertainty at the respective positions across the object, each predicted uncertainty value being a predicted measure, at a respective position, of the standard deviation in the corresponding ADC value at that position. The input to the neural network includes the ADC map or the data from which the ADC map is derivable, and the output is the predicted uncertainty map.

IPC Classes  ?

• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography

Abstract

The present invention provides a method for predicting whether a human subject having breast cancer will respond to aromatase inhibitor (Al) therapy, the method comprising : a ) measuring the gene expression in a sample obtained from the subject to obtain a sample gene expression profile of the breast tumour of at least the following genes : CHAD, NAT1, SLC39A6, BCL2, IGF1R, ESRI, GRB7 and ERBB2; b ) assigning the sample to one of a plurality of predetermined clusters based on the similarity of the sample gene expression profile to the gene expression centroids of said clusters; and c ) making a prediction of whether the subject will respond to said Al therapy based on the cluster to which the sample is assigned. Also provided are related methods of treatment, computer-implemented methods of predicting treatment response and systems for use in such methods.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• A61K 31/4196 - 1,2,4-Triazoles

Abstract

The disclosure is in part directed to a method of treating a cancer in a patient in need thereof, comprising administering to the patient an effective amount of a HSF1 pathway inhibitor, wherein the cancer comprises solid tumors identified as having an ARID 1 A mutation.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 35/00 - Antineoplastic agents
• A61P 35/02 - Antineoplastic agents specific for leukemia
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The present invention relates to salts and polymorphic forms of Compound A (6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine), an inhibitor of Aurora kinase and FMS-like tyrosine kinase 3 (FLT3) activity. The present invention also relates to processes for the preparation of the salts and polymorphic forms of the compound, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and/or FLT3 activity is implicated.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems

Abstract

The present invention relates to formulations comprising a compound of Formula (1) (6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine) which is an inhibitor of Aurora kinase enzyme activity and FMS-like tyrosine kinase 3 (FLT3) activity, and a non-ionic surfactant. The present invention also relates to processes for the preparation of the formulations of the compound, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and/or FLT3 activity is implicated.

IPC Classes  ?

• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
• A61K 9/20 - Pills, lozenges or tablets
• A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• A61K 47/10 - AlcoholsPhenolsSalts thereof, e.g. glycerolPolyethylene glycols [PEG]PoloxamersPEG/POE alkyl ethers

Abstract

The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula (I): The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula (I): The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula (I): or a pharmaceutically acceptable salt thereof, wherein the medicament is used in such a manner that: (a) said compound or salt is administered twice weekly for 3 weeks, (b) administration of said compound or salt is paused for the following 1 week, and (c) steps (a) and (b) are subsequently repeated at least once.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

Provided are compounds of the Formula (I), or a pharmaceutically acceptable salt thereof: 3, x and n are defined in the specification. The compounds are inhibitors of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family members (LOXL1, LOXL2, LOXL3, LOXL4) and are useful in therapy, particularly in the treatment of cancer. Also disclosed are LOX inhibitors for use in the treatment of a cancer associated with EGFR and biomarkers that predict responsiveness to a LOX inhibitor.

IPC Classes  ?

• C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61P 35/00 - Antineoplastic agents
• C07D 263/46 - Sulfur atoms
• C07D 277/26 - Radicals substituted by sulfur atoms
• C07D 277/36 - Sulfur atoms
• C07D 333/18 - Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
• C07D 333/34 - Sulfur atoms
• C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase

Abstract

Methods and systems for analysing the cellular composition of a sample are described, comprising: providing an image of the sample in which a plurality of cellular populations are associated with respective signals and classifying a plurality of query cells in the image between a plurality of classes corresponding to respective cellular populations in the plurality of cellular populations. This is performed by providing a query single cell image to an encoder module of a machine learning model to produce a feature vector for the query image, and assigning the query cell to one of the plurality of classes based on the feature vector for the query image and feature vectors produced by the encoder module for each of a plurality of reference single cell images. The machine leaning model comprises: the encoder module, configured to take as input a single cell image and to produce as output a feature vector the single cell image, and a similarity module configured to take as input a pair of feature vectors for a pair of single cell images and to produce as output a score indicative of the similarity between the single cell images. Thus, the machine learning model can be obtained without the need for an extensively annotated dataset. The methods find use in the analysis of multiplex immunohistochemistry / immunofluorescence in a variety of clinical contexts.

IPC Classes  ?

• G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
• G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks

Abstract

A method of performing diffusion-weighted magnetic resonance imaging is provided. The method includes a step of: using a neural network to filter a diffusion-weighted image of an object acquired by a magnetic resonance imaging scanner, the neural network being programmed to produce an output image from the acquired image. The neural network improves the signal to noise ratio of the output image relative to the acquired image. The neural network, when applied to a synthetic knife-edge image to which Rician noise providing a signal-to-noise ratio of 13 or more is added, forms a curve of normalised values of modulation-transfer-function against frequency which has a higher area thereunder than the area under the corresponding curve of normalised values of modulation-transfer-function against frequency for a reference Gaussian smoothing filter.

IPC Classes  ?

• G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01R 33/561 - Image enhancement or correction, e.g. subtraction or averaging techniques by reduction of the scanning time, i.e. fast acquiring systems, e.g. using echo-planar pulse sequences
• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography
• G06N 3/08 - Learning methods

Abstract

This invention relates to compounds useful as lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family member (LOXL1, LOXL2, LOXL3, LOXL4) inhibitors. In addition there are contemplated pharmaceutical compositions comprising the compounds and the use of the compounds in the treatment of conditions mediated by LOX and LOXL, for example cancer. In particular a LOX inhibitor such as the present compounds may be for use in the treatment of a cancer associated with EGFR. The present invention also contemplates the identification of biomarkers that predict responsiveness to a LOX inhibitor.

IPC Classes  ?

• C07D 471/08 - Bridged systems
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
• A61P 35/00 - Antineoplastic agents
• C07D 487/08 - Bridged systems

Abstract

t where:formula (I), k, ρ and c denoting respectively the heat conductivity, the density and the heat capacity of the target material, and d denoting the electron penetration depth in the target material. ,

IPC Classes  ?

• H01J 35/00 - X-ray tubes
• H01J 35/26 - Tubes wherein the point of impact of the cathode ray on the anode or anticathode is movable relative to the surface thereof by rotation of the anode or anticathode
• G21K 1/02 - Arrangements for handling particles or ionising radiation, e.g. focusing or moderating using diaphragms, collimators
• G21K 1/087 - Deviation, concentration, or focusing of the beam by electric or magnetic means by electrical means
• H01J 35/10 - Rotary anodesArrangements for rotating anodesCooling rotary anodes
• H01J 35/14 - Arrangements for concentrating, focusing, or directing the cathode ray

Abstract

The invention relates to methods for treating prostate cancer by targeting the generation of splice variants of the androgen receptor. In one aspect, this can be achieved by targeting JMJD6 to reduce the production of androgen receptor splice variants. The invention finds particular use in the treatment of prostate cancer that is resistant to conventional androgen therapy.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 31/194 - Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• A61P 35/00 - Antineoplastic agents

Abstract

The invention relates to methods for treating prostate cancer by targeting the generation of splice variants of the androgen receptor. In one aspect, this can be achieved by targeting JMJD6 to reduce the production of androgen receptor splice variants. The invention finds particular use in the treatment of prostate cancer that is resistant to conventional androgen therapy.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/194 - Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

HORMAD1HORMAD1 with an agent that modulates mitotic processes, and diagnostic methods thereof.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention provides a method for predicting whether a human subject having breast cancer will be resistant to, or sensitive to, therapy with a eye1in-dependent kinase (CDK) inhibitor, the method comprising: a) measuring the gene expression in a sample obtained from the breast tumour of the patient to obtain a sample gene expression profile of at least the following modules: (i) a luminal vs. non-luminal module comprising at least four genes selected from the group consisting of: ACTR3B, ANLN, BAG1, BCL2, BIRC5, BLVRA, CCNB1, CCNE1, CDC20, CDC6, CDCA1, CDH3, CENPF, CEP55, CXXC5, EGFR, ERBB2, ESR1, EX01, FGFR4, F0XA1, F0XC1, GPR160, GRB7, KIF2C, KRT14, KNTC2, KRT17, KRT5, MAPT, MDM2, MELK, MIA, MKI67, MLPH, MMP11, MYBL2, MYC, NAT1, 0RC6L, PGR, PHGDH, PTTG1, RRM2, SFRP1, SLC39A6, TMEM45B, TYMS, UBE2C and UBE2T; (ii) a E2F module comprising at least five genes selected from the group consisting of: ARHGAP11A, ATAD2, C10ORF119, CASP8AP2, CLSPN, DCK, DNAJC9, FANGD2, FBX05, FKBP5, H2AFZ, KIAA0101, KPNB1, NUP62, RANBP1, RET, SFRS1, SFRS10, SFRS7, SNRPD1, STMN1 and TMPO; (ill) an RBI module comprising the gene RB1; and (iv) a CCNE1 module comprising the gene CCNE1; and b) making a prediction of whether the subject will be resistant to or sensitive to said CDK inhibitor treatment based on the sample gene expression profile comprising said modules (i) to (iv). Also provided are related methods of treatment, computer-implemented methods of predicting treatment response and systems for use in such methods.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

The present invention provides a method for predicting the treatment response of a human bladder cancer patient, the method comprising: a) measuring the gene expression of at least 9, at least 10, at least 15, at least 20 or at least 30 of the genes from Group 1 in Table 10 and at least 1, at least 2, at least 3 or at least 5 of the genes from Groups 2-4 in Table 10 in a sample obtained from the bladder tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Related methods and systems are also described. The invention finds particular use in predicting whether a bladder cancer patient is likely to be sensitive to (chemo)radiation therapy.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The disclosure relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, Formula (I) as defined herein. Compounds according to Formula I are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer. The disclosure relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, Formula (I) as defined herein. Compounds according to Formula I are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer.

IPC Classes  ?

• C07D 471/08 - Bridged systems
• C07D 487/08 - Bridged systems
• C07D 295/088 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
• C07D 487/04 - Ortho-condensed systems
• C07D 239/48 - Two nitrogen atoms
• C07D 295/108 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulfur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
• C07D 487/10 - Spiro-condensed systems
• A61P 35/00 - Antineoplastic agents

Abstract

The dose and regimen of the sensitizer of the present invention which is effective for anticancer therapy for tumors and the schedule of the anticancer therapy, such as radiotherapy and anticancer chemotherapy, wihch is effective after administration of the sensitizer, are still unclear. The present inventors have demonstrated that the sensitizer for anticancer therapy, which is prepared by combining a specific range of concentration of H2O2 with a specific range of concentration of hyaluronic acid or a salt thereof in a specific amount, in a specific procedure, can be injected into the the affected tumor site to improve the effect of anticancer therapy such as radiation therapy and anticancer chemotherapy, thereby solving the above problems.

IPC Classes  ?

• A61K 33/40 - Peroxides
• A61K 31/728 - Hyaluronic acid

Abstract

The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and/or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and/or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and/or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and/or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula or a pharmaceutically acceptable salt thereof, wherein the medicament is used in such a manner that: (a) said compound or salt is administered twice weekly for 3 weeks, (b) administration of said compound or salt is paused for the following 1 week, and (c) steps (a) and (b) are subsequently repeated at least once.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

The present invention relates to salts and polymorphic forms of Compound A (6-chloro-7-(4-(4- chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine), an inhibitor of Aurora kinase and FMS-like tyrosine kinase 3 (FLT3) activity. The present invention also relates to processes for the preparation of the salts and polymorphic forms of the compound, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and/or FLT3 activity is implicated.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems

Abstract

The present invention relates to formulations comprising a compound of Formula (1) (6-chloro-7-(4-(4- chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine) which is an inhibitor of Aurora kinase enzyme activity and FMS-like tyrosine kinase 3 (FLT3) activity, and a non-ionic surfactant. The present invention also relates to processes for the preparation of the formulations of the compound, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and/or FLT3 activity is implicated.

IPC Classes  ?

• A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate

Abstract

The present invention relates to salts and polymorphic forms of Compound A (6-chloro-7-(4-(4- chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine), an inhibitor of Aurora kinase and FMS-like tyrosine kinase 3 (FLT3) activity. The present invention also relates to processes for the preparation of the salts and polymorphic forms of the compound, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and/or FLT3 activity is implicated.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 35/00 - Antineoplastic agents

Abstract

3 are as defined herein. Compounds according to Formula (I) are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• C07D 487/04 - Ortho-condensed systems

Abstract

The invention relates to methods of determining and tracking tumour evolution using the methylation signature of ctDNA. The invention also relates to methods and kits for determining a phylogenetic relationship between different tumours in a patient and evaluating the effectiveness of treatment regimes.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention relates to compounds of Formula I as defined herein, and salts and solvates thereof. (I) The present invention also relates to pharmaceutical compositions comprising compounds of Formula (I), and to compounds of Formula (I) for use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which inhibition of a RAS-effector protein-protein interaction is implicated.

IPC Classes  ?

• C07D 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C07C 217/92 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the nitrogen atom of at least one of the amino groups being further bound to a carbon atom of a six-membered aromatic ring
• C07C 237/30 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
• C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals

Abstract

5 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 471/04 - Ortho-condensed systems
• C07D 471/10 - Spiro-condensed systems
• C07D 491/10 - Spiro-condensed systems
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: 31 and Ring A are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• A61P 35/00 - Antineoplastic agents
• C07D 471/04 - Ortho-condensed systems
• C07D 498/14 - Ortho-condensed systems
• C07D 498/20 - Spiro-condensed systems
• C07D 513/04 - Ortho-condensed systems
• C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or

Abstract

3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 471/04 - Ortho-condensed systems
• C07D 471/08 - Bridged systems
• C07D 487/04 - Ortho-condensed systems

Abstract

The present invention relates to compounds that function as inhibitors of BCL6 (B-cell lymphoma 6) activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to compounds that function as inhibitors of BCL6 (B-cell lymphoma 6) activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or

Abstract

f(x, y)f(x, y) is the noisy synthetic knife-edge image, g(x, y) is the filtered image, [Formula II should be inserted here] is the convolution parameter, and σ2is the smoothing variance set such that σ2 = 4.

IPC Classes  ?

• G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques
• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CH5126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CH5126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

Provided are compounds of the Formula (I), or a pharmaceutically acceptable salt thereof: 3, x and n are defined in the specification. The compounds are inhibitors of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family members (LOXL1, LOXL2, LOXL3, LOXL4) and are useful in therapy, particularly in the treatment of cancer. Also disclosed are LOX inhibitors for use in the treatment of a cancer associated with EGFR and biomarkers that predict responsiveness to a LOX inhibitor.

IPC Classes  ?

• C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61P 35/00 - Antineoplastic agents
• C07D 263/46 - Sulfur atoms
• C07D 277/46 - Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
• C07D 277/36 - Sulfur atoms
• C07D 333/18 - Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
• C07D 333/34 - Sulfur atoms
• C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
• C07D 277/26 - Radicals substituted by sulfur atoms

Abstract

The present invention relates to compounds of Formula I as defined herein, and salts and solvates thereof. (I) The present invention also relates to pharmaceutical compositions comprising compounds of Formula (I), and to compounds of Formula (I) for use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which inhibition of a RAS-effector protein-protein interaction is implicated.

IPC Classes  ?

• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 319/18 - Ethylenedioxybenzenes, not substituted on the hetero ring
• C07D 319/20 - 1,4-DioxanesHydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
• C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 471/10 - Spiro-condensed systems

Abstract

The invention relates to the field of cancer. In particular, to patient selection methods and methods of treating cancers that employ a synthetic lethality approach, whereby cancers which are deficient in homologous recombination (HR) are preferentially killed when treated with an agent capable of inhibiting EXD2. The invention also provides methods for screening for EXD2 inhibitors for use in the methods of treatment of the invention.

IPC Classes  ?

• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• A61K 31/194 - Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• A61P 35/00 - Antineoplastic agents

Abstract

This invention relates to compounds useful as lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family member (LOXL1, LOXL2, LOXL3, LOXL4) inhibitors. In addition there are contemplated pharmaceutical compositions comprising the compounds and the use of the compounds in the treatment of conditions mediated by LOX and LOXL, for example cancer. In particular a LOX inhibitor such as the present compounds may be for use in the treatment of a cancer associated with EGFR. The present invention also contemplates the identification of biomarkers that predict responsiveness to a LOX inhibitor.

IPC Classes  ?

• C07D 471/08 - Bridged systems
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
• A61P 35/00 - Antineoplastic agents
• C07D 487/08 - Bridged systems

Abstract

The present invention provides a method for predicting the treatment response of a human gastroesophageal cancer patient, the method comprising: a) measuring the gene expression of at least 3 of the following genes: CDH1, CDK6, COX2, ELOVL5, GATA4, EGFR, TBCEL, FGF7, CDH17, FNBP1, PIP5K1B, TWIST, CD44, MET, CEACAM1, TOX3, GLIPR2, GSTP1, RON, TMEM136, MYB, BRCA2, FGF1, POU5F1, EPR, DPYD, ABL2 and SH3RF1 in a sample obtained from the gastroesophageal tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Also provided are related computer-implemented methods and methods of treatment of gastroesophageal cancer.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

A method of producing a magnetic resonance (MR) image of a region of interest is provided. The method includes the steps of: acquiring an initial MR image of the region of interest, the initial MR image mapping values of an MR-sensitive, physical property at positions over the region; determining a corresponding map of the estimated uncertainties in the values of the MR-sensitive, physical property over the region; and calculating a weighted MR image of the region, the weighted MR image mapping values of a function which combines, at each position of the initial image, the respective value of the MR-sensitive, physical property and the respective estimated uncertainty, the function applying a higher weighting to positions with relatively low estimated uncertainties than to positions with relatively high estimated uncertainties.

IPC Classes  ?

• G06K 9/00 - Methods or arrangements for reading or recognising printed or written characters or for recognising patterns, e.g. fingerprints
• G06T 11/00 - 2D [Two Dimensional] image generation
• G01R 33/483 - NMR imaging systems with selection of signal or spectra from particular regions of the volume, e.g. in vivo spectroscopy
• G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques
• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography
• G06T 7/00 - Image analysis

Abstract

The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of an MPS1 inhibitor, wherein: (i) said subject has previously been treated with an endocrine therapy; and/or (ii) said breast cancer is resistant to endocrine therapy.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/565 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: Formula (I) wherein X, R1, R2, and R3are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6activity is implicated.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 471/04 - Ortho-condensed systems
• C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles

Abstract

The disclosure relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, Formula (I) as defined herein. Compounds according to Formula I are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer.

IPC Classes  ?

• C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 487/04 - Ortho-condensed systems
• C07D 487/08 - Bridged systems
• C07D 487/10 - Spiro-condensed systems
• A61P 35/00 - Antineoplastic agents
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine

Abstract

(ii) said breast cancer is resistant to treatment with a CDK4/6 inhibitor.

IPC Classes  ?

• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides a method of treatment of prostate cancer, comprising administering a therapeutically effective amount of an inhibitor of IL-23 and/or an inhibitor of IL-23R to a mammalian patient in need thereof. The prostate cancer may be castration resistant prostate cancer (CRPC). The inhibitor may, for example, be an anti-IL-23 antibody, such as risankizumab, guselkumab or tildrakizumab. The method of treatment may further comprise administration of androgen deprivation therapy, such as enzalutamide. Also provided is a method of predicting the development of resistance to androgen deprivation therapy (ADT) in a prostate cancer in a mammalian patient and a related screening method.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

The disclosure relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein X1 and X5 is each selected from CR1 or N; X2, X3 and X4 is each selected from CR1, CR2 or N, provided at least one of X2, X3 and X4 is CR2 and provided only one of X1, X2, X3, X4 and X5 can be N. R1, R2, R3, R4, R5, L1, L2 and L3 are as defined herein. Compounds according to Formula (I) are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
• A61P 35/00 - Antineoplastic agents

Abstract

The disclosure relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein X1and X5is each selected from CR1or N; X2,X3and X4is each selected from CR1, CR2or N, provided at least one of X2, X3and X4is CR2and provided only one of X1, X2, X3, X4and X5can be N. R1, R2, R3, R4, R5, L1, L2and L3 are as defined herein. Compounds according to Formula (I) are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61P 35/00 - Antineoplastic agents
• A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine

Abstract

Materials and methods for monitoring the development of resistance of cancers to treatment The present invention relates to materials and methods for monitoring and treating cancers and to methods of identifying/detecting/monitoring the development of resistance of cancers to tyrosine kinase inhibitors.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity Formula (I) wherein X1, X2, R1, R2, R30, R31 and Ring A are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5513 - 1,4-Benzodiazepines, e.g. diazepam
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• A61P 35/00 - Antineoplastic agents
• C07D 471/04 - Ortho-condensed systems
• C07D 498/08 - Bridged systems
• C07D 498/20 - Spiro-condensed systems
• C07D 513/04 - Ortho-condensed systems

Abstract

122, R1, R2, R30, R31 and Ring A are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• C07D 498/08 - Bridged systems
• C07D 498/20 - Spiro-condensed systems
• C07D 513/04 - Ortho-condensed systems
• C07D 471/04 - Ortho-condensed systems
• A61K 31/5513 - 1,4-Benzodiazepines, e.g. diazepam
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to methods for predicting prognosis and overall survival among tumour/cancer patients, and methods for classifying and stratifying these patients, particularly patients having pancreatic neuroendocrine tumors (PanNETs). The invention also relates to therapeutic methods for treating classified patients. Measuring gene expression levels of at least some of a selected group 198 genes is shown to be useful in the stratification of patients into groups with prognostic significance, and making a prediction of prognosis.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

t where: formula (I), k, ρ and c denoting respectively the heat conductivity, the density and the heat capacity of the target material, and d denoting the electron penetration depth in the target material. )

IPC Classes  ?

• H01J 35/00 - X-ray tubes
• H01J 35/26 - Tubes wherein the point of impact of the cathode ray on the anode or anticathode is movable relative to the surface thereof by rotation of the anode or anticathode
• G21K 1/02 - Arrangements for handling particles or ionising radiation, e.g. focusing or moderating using diaphragms, collimators
• G21K 1/087 - Deviation, concentration, or focusing of the beam by electric or magnetic means by electrical means
• H01J 35/10 - Rotary anodesArrangements for rotating anodesCooling rotary anodes
• H01J 35/14 - Arrangements for concentrating, focusing, or directing the cathode ray

Abstract

The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, wherein the medicament is used in such a manner that: (a) said compound or salt is administered twice weekly for 3 weeks, (b) administration of said compound or salt is paused for the following 1 week, and (c) steps (a) and (b) are subsequently repeated at least once.

IPC Classes  ?

• A61K 31/37 - Coumarins, e.g. psoralen
• A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• A61P 35/04 - Antineoplastic agents specific for metastasis
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula or a pharmaceutically acceptable salt thereof, wherein the medicament is used in such a manner that: (a) said compound or salt is administered twice weekly for 3 weeks, (b) administration of said compound or salt is paused for the following 1 week, and (c) steps (a) and (b) are subsequently repeated at least once.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• A61P 35/00 - Antineoplastic agents

Abstract

Provided are compounds of the Formula (I), or a pharmaceutically acceptable salt thereof: 3, x and n are defined in the specification. The compounds are inhibitors of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family members (LOXL1, LOXL2, LOXL3, LOXL4) and are useful in therapy, particularly in the treatment of cancer. Also disclosed are LOX inhibitors for use in the treatment of a cancer associated with EGFR and biomarkers that predict responsiveness to a LOX inhibitor.

IPC Classes  ?

• C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61P 35/00 - Antineoplastic agents
• C07D 333/18 - Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
• C07D 277/26 - Radicals substituted by sulfur atoms
• C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
• C07D 333/34 - Sulfur atoms
• C07D 277/36 - Sulfur atoms
• C07D 263/46 - Sulfur atoms
• C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula or a pharmaceutically acceptable salt thereof, wherein the medicament is used in such a manner that: (a) said compound or salt is administered twice weekly for 3 weeks, (b) administration of said compound or salt is paused for the following 1 week, and (c) steps (a) and (b) are subsequently repeated at least once.

IPC Classes  ?

• A61K 31/37 - Coumarins, e.g. psoralen
• A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• A61P 35/04 - Antineoplastic agents specific for metastasis
• A61P 35/00 - Antineoplastic agents

Abstract

This invention relates to compounds useful as lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family member (LOXL1, LOXL2, LOXL3, LOXL4) inhibitors. In addition there are contemplated pharmaceutical compositions comprising the compounds and the use of the compounds in the treatment of conditions mediated by LOX and LOXL, for example cancer. In particular a LOX inhibitor such as the present compounds may be for use in the treatment of a cancer associated with EGFR. The present invention also contemplates the identification of biomarkers that predict responsiveness to a LOX inhibitor.

IPC Classes  ?

• C07D 471/08 - Bridged systems
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
• A61P 35/00 - Antineoplastic agents

Abstract

This invention relates to compounds useful as lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family member (LOXL1, LOXL2, LOXL3, LOXL4) inhibitors. In addition there are contemplated pharmaceutical compositions comprising the compounds and the use of the compounds in the treatment of conditions mediated by LOX and LOXL, for example cancer. In particular a LOX inhibitor such as the present compounds may be for use in the treatment of a cancer associated with EGFR. The present invention also contemplates the identification of biomarkers that predict responsiveness to a LOX inhibitor.

IPC Classes  ?

• C07D 471/08 - Bridged systems
• A61P 35/00 - Antineoplastic agents
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine

Abstract

The present invention provides a method for predicting the treatment response of a human gastroesophageal cancer patient, the method comprising: a) measuring the gene expression of at least 3 of the following genes: CDH1, CDK6, COX2, ELOVL5, GATA4, EGFR, TBCEL, FGF7, CDH17, FNBP1, PIP5K1B, TWIST, CD44, MET, CEACAM1, TOX3, GLIPR2, GSTP1, RON, TMEM136, MYB, BRCA2, FGF1, POU5F1, EPR, DPYD, ABL2 and SH3RF1 in a sample obtained from the gastroesophageal tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Also provided are related computer-implemented methods and methods of treatment of gastroesophageal cancer.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention provides a method for predicting the treatment response of a human gastroesophageal cancer patient, the method comprising: a) measuring the gene expression of at least 3 of the following genes: CDH1, CDK6, COX2, ELOVL5, GATA4, EGFR, TBCEL, FGF7, CDH17, FNBP1, PIP5K1B, TWIST, CD44, MET, CEACAM1, TOX3, GLIPR2, GSTP1, RON, TMEM136, MYB, BRCA2, FGF1, POU5F1, EPR, DPYD, ABL2 and SH3RF1 in a sample obtained from the gastroesophageal tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Also provided are related computer-implemented methods and methods of treatment of gastroesophageal cancer.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention relates to materials and methods for stratifying and treating cancers and to methods of identifying/selecting patients for treatment of cancer with tyrosine kinase inhibitors. Gene expression profiles, TP53 mutations and FGFR1 and PDGFRA expression are used to identify/select/stratify the cancers and patients.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of an MPS1 inhibitor, wherein: (i) said subject has previously been treated with an endocrine therapy; and/or (ii) said breast cancer is resistant to endocrine therapy.

IPC Classes  ?

• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/52 - Purines, e.g. adenine
• A61K 31/565 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol
• A61P 35/00 - Antineoplastic agents

Abstract

The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound capable of inhibiting MPS1, wherein: (i) said subject has previously been treated with a CDK4/6 inhibitor; and/or (ii) said breast cancer is resistant to treatment with a CDK4/6 inhibitor.

IPC Classes  ?

• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/52 - Purines, e.g. adenine
• A61K 31/565 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol
• A61P 35/00 - Antineoplastic agents

Abstract

The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of an MPS1 inhibitor, wherein: (i) said subject has previously been treated with an endocrine therapy; and/or (ii) said breast cancer is resistant to endocrine therapy.

IPC Classes  ?

• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/52 - Purines, e.g. adenine
• A61K 31/565 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol
• A61P 35/00 - Antineoplastic agents

Abstract

The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound capable of inhibiting MPS1, wherein: (i) said subject has previously been treated with a CDK4/6 inhibitor; and/or (ii) said breast cancer is resistant to treatment with a CDK4/6 inhibitor.

IPC Classes  ?

• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/52 - Purines, e.g. adenine
• A61K 31/565 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol
• A61P 35/00 - Antineoplastic agents

Abstract

The use of cyclin dependent kinase 4/6 inhibitors in methods of treating an individual with a cancer characterised by CREB-binding protein deficiency and/or up-regulation of FOXM1 expression is disclosed along with corresponding methods of selecting and treating patients for treatment.

IPC Classes  ?

• A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

The use of poly ADP ribose polymerase (PARP) inhibitors the treatment of cancer which is mutated or deficient in the SF3B gene is described based on findings indicating that mutations in SF3B1aretherapeutically tractable in cancers using PARP inhibitors and show an impaired response to DNA damage.

IPC Classes  ?

• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents
• A61P 35/02 - Antineoplastic agents specific for leukemia
• G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups

Abstract

The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X1, X2, R1, R2 and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 35/00 - Antineoplastic agents
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 487/04 - Ortho-condensed systems

Abstract

The present invention relates to compounds of formula I that function as inhibitors of BCL6(B- cell lymphoma 6) activity: Formula I wherein X1, X2, X3, R1, R2, R3, R4 and R5 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer,as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 215/42 - Nitrogen atoms attached in position 4
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61P 35/00 - Antineoplastic agents
• A61K 31/4704 - 2-Quinolinones, e.g. carbostyril

Abstract

The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X1, X2, R1, R2 and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles

Goods & Services

Maintaining, updating and managing data within computer and online databases. Provision of education and training in the field of medical research, scientific research, drug discovery, pharmaceutical research and pharmaceutical development; educational information in the field of medical research, scientific research, drug discovery, pharmaceutical research and pharmaceutical development provided on-line from a computer database or the internet; organising conferences, symposiums or exhibitions in the field of medical research, scientific research, drug discovery, pharmaceutical research and pharmaceutical development; online research library services. Providing online information in the field of medical research, medical treatments research, scientific research, drug discovery, pharmaceutical research and pharmaceutical development, from a computer database.

Abstract

The present invention provides a composition comprising a Checkpoint (Chk1) inhibitor for use in a method of treatment of a cancer in a mammalian subject, wherein the cancer comprises one or more cells that carry mutations in or are deficient in DNA polymerase alpha and/or DNA polymerase epsilon. Also provided is a composition comprising a Checkpoint 1 (Chk1) inhibitor for use in a method of treatment of a cancer in a mammalian subject, wherein the Chk inhibitor is administered simultaneously, separately or sequentially with an inhibitor of DNA polymerase epsilon. Related methods of treatment are also provided.

IPC Classes  ?

• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61P 35/00 - Antineoplastic agents

Goods & Services

(1) Maintaining, updating and managing data within computer and online databases (2) Provision of education and training in the field of medical research, drug discovery, pharmaceutical research, pharmaceutical development and scientific research in the fields of breast cancer, cancer biology, cancer therapeutics, clinical studies, genetics and epidemiology, molecular pathology, radiotherapy and imaging and structural biology; educational information in the field of medical research, drug discovery, pharmaceutical research, pharmaceutical development and scientific research in the fields of breast cancer, cancer biology, cancer therapeutics, clinical studies, genetics and epidemiology, molecular pathology, radiotherapy and imaging and structural biology, provided on-line from a computer database and the internet; organising conferences, symposiums and exhibitions in the field of medical research, drug discovery, pharmaceutical research, pharmaceutical development and scientific research in the fields of breast cancer, cancer biology, cancer therapeutics, clinical studies, genetics and epidemiology, molecular pathology, radiotherapy and imaging and structural biology; online research library services (3) Operation of an online computer database in the field of medical research, drug discovery, pharmaceutical research, pharmaceutical development and scientific research in the fields of breast cancer, cancer biology, cancer therapeutics, clinical studies, genetics and epidemiology, molecular pathology, radiotherapy and imaging and structural biology; providing information in the field of medical research, drug discovery, pharmaceutical research, pharmaceutical development and scientific research in the fields of breast cancer, cancer biology, cancer therapeutics, clinical studies, genetics and epidemiology, molecular pathology, radiotherapy and imaging and structural biology via an online database; (4) Providing information in the field of oncological medical treatments via an online database; operation of an online computer database in the field of oncological medical treatments;