A method of treating locally advanced or metastatic renal cell carcinoma in a subject in need thereof and selecting patients to be treated for cancer, the method comprising: analyzing a tumor sample from a human cancer patient for an expression level of HIF-1α and an expression level of HIF-2α; administering to the human cancer patient an effective amount of a HIF-2α antagonist and an effective amount of the compound of formula (I): when the tumor sample expresses both HIF-1α and HIF-2α, or a pharmaceutically acceptable salt thereof and belzutifan.
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
2.
METHODS OF TREATING ACUTE MYELOID LEUKEMIA USING COMBINATIONS OF GCN2 MODULATORS, VENETOCLAX, AND AZACITIDINE
Provided herein are methods of treating acute myeloid leukemia (AML) in a subject in need thereof, comprising administering to the subject combinations of Compound 1, or a pharmaceutically acceptable salt thereof, venetoclax, and 5-azacitidine. Also provided herein are methods of inhibiting/overcoming resistance of AML to venetoclax in a subject in need thereof, and/or improving the efficacy of venetoclax in the treatment of AML in a subject in need thereof, comprising administering to the subject combinations of Compound 1, or a pharmaceutically acceptable salt thereof, venetoclax, and 5-azacitidine.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 31/706 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
A61P 35/02 - Antineoplastic agents specific for leukemia
3.
BETA-GLUCAN METHODS AND COMPOSITIONS THAT AFFECT THE TUMOR MICROENVIRONMENT
This disclosure relates to the combination of soluble β-glucan and immune suppression-relieving agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-angiogenics, checkpoint inhibitors including non-tumor targeting antibodies.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
The present invention relates to the combination of soluble β-glucan and anti-cancer agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-cancer agents.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
5.
BETA-GLUCAN IMMUNOTHERAPIES AFFECTING THE IMMUNE MICROENVIRONMENT
This disclosure relates to soluble β-glucan immunotherapies that affect the tumor microenvironment. The soluble β-glucan immunotherapies promote an immunostimulatory environment, which enhances the effectiveness of the combination of anti-angiogenics and checkpoint inhibitors.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
6.
BETA-GLUCAN IN COMBINATION WITH ANTI-CANCER AGENTS AFFECTING THE TUMOR MICROENVIRONMENT
The present invention relates to the combination of soluble β-glucan and anti-cancer agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-cancer agents.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
A61K 39/00 - Medicinal preparations containing antigens or antibodies
7.
N-ISOPROPYLNICOTINAMIDE AND METHODS FOR USING THE SAME
Provided herein are crystalline forms of a compound of formula (I) and pharmaceutical compositions thereof. Also provided herein are methods of using the crystalline forms and pharmaceutical compositions to treat a cancer and viruses (e.g., coronaviruses), and other diseases and disorders involving protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK).
CRYSTALLINE FORMS OF 6-(3-((5-CHLORO-2-METHOXYPYRIDINE)-3- SULFONAMIDO)-2,6-DIFLUOROPHENYL)-N-METHYLIMIDAZO[L,5- AJPYRAZINE-L-CARBOXAMIDE AND METHODS FOR USING THE SAME
Provided herein are crystalline forms of a compound of formula (I) and pharmaceutical compositions thereof. Also provided herein are methods of using the crystalline forms and pharmaceutical compositions to treat a cancer or a neurodegenerative disease in a subject in need thereof.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula: (T) where A, B, R1, X1, X2, and W are described herein.
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula: (T) where A, B, R1, X1, X2, and W are described herein.
C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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 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 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 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 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
Provided herein are compounds, compositions, and methods useful for modulating the activity of GCN2 and for treating related conditions, diseases, and disorders (e.g., cancer and neurodegenerative diseases).
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
Provided herein are methods of inhibiting myeloid-derived suppressor cells (MDSCs) in a subject in need thereof administering the GCN2 inhibitor of formula (I). The present disclosure also provides methods of treating or reducing the tumor volumes of metastases in a subject in need thereof administering the GCN2 inhibitor of formula (I).
Provided herein are methods of treating a cancer (e.g., a solid tumor) in a subject in need thereof. The present disclosure also provides methods of activating the immune system of a subject in need thereof (e.g., a subject having a cancer). The methods described herein generally comprise administering to the subject an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and an immunotherapy (e.g., an anti-PD-1 antibody) and/or an antiangiogenic agent (e.g., VEGFR-TKI).
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 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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
Provided herein are compounds, compositions, and methods useful for modulating the activity of GCN2 and for treating related conditions, diseases, and disorders (e.g., cancer and neurodegenerative diseases).
This disclosure provides, in one aspect, dosing strategies for soluble β-glucan immunotherapy to optimize acute immunopharmacodynamic responses for the immunotherapy and/or subject. It also provides a method for analyzing a sample from a subject for a biomarker to identify the appropriate dosing strategy for soluble β-glucan immunotherapy. Generally, the method includes obtaining a biological sample from a subject, analyzing the sample for a biomarker anti-β-glucan antibody level or immunopharmacodynamic response level, classifying the subject into a subgroup based on the biomarker anti-β-glucan antibody level or immunopharmacodynamic response level and identifying the appropriate dosing strategy based on the subgroup classification.
Provided herein are methods of treating advanced solid tumors in a subject in need thereof, for example, when the subject has advanced squamous cell carcinoma of the head and neck, colorectal cancer, non-small cell lung cancer, and transitional cell carcinoma of the bladder. Also provided herein are methods of treating blood cancers, such as acute myeloid leukemia, in a subject in need thereof.
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 39/00 - Medicinal preparations containing antigens or antibodies
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
The present disclosure provides methods of treating or preventing various conditions, diseases, and disorders (e.g., cancer, sepsis/septicemia, pneumonia, fungal infection, immunoparalysis, COVID-19, and myeloablation) in a subject in need thereof by administering to the subject a therapeutically effective amount of a soluble β-glucan, whereby the soluble β-glucan induces trained immunity in the subject. In particular, the methods provided herein are useful for treating or preventing conditions associated with cancer (e.g., sepsis/septicemia, pneumonia, fungal infection, immunoparalysis) and/or the treatment of cancer (e.g., administration of a chemotherapeutic agent and/or radiation therapy).
This disclosure relates to soluble β-glucan immunotherapies that affect the tumor microenvironment. The soluble β-glucan immunotherapies promote an immunostimulatory environment, which enhances the effectiveness of the combination of anti-angiogenics and checkpoint inhibitors.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
19.
(AZA)INDAZOLYL-ARYL SULFONAMIDE AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS
The invention provides (aza)indazolyl-aryl sulfonamide and related compounds, pharmaceutical compositions, and their use in the treatment of medical conditions, such as cancer, and in inhibiting GCN2 activity.
C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
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 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 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 401/12 - 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 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 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 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
20.
Aminopyrimidine derivatives as phosphatidylinositol phosphate kinase inhibitors
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula:
2, and W are described herein.
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 491/056 - Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
C07D 401/04 - 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 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 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 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
C07D 241/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
Provided herein are compounds, compositions, and methods useful for modulating the activity of GCN2 and for treating related conditions, diseases, and disorders (e.g., cancer and neurodegenerative diseases).
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 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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
Provided herein are compounds, compositions, and methods useful for modulating the activity of GCN2 and for treating related conditions, diseases, and disorders (e.g., cancer and neurodegenerative diseases).
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
27.
Methods for identifying beta-glucan binding to immune cells
This disclosure describes, in one aspect, a method for identifying β-glucan binding to immune cells of a subject. Generally, the method includes obtaining a blood sample from the subject, the blood sample comprising immune cells, adding soluble β-glucan to at least a portion of the blood sample and incubating the mixture under conditions allowing the soluble β-glucan to bind to the immune cells, and detecting soluble β-glucan hound to the immune cells. In another aspect, this disclosure describes a method that generally includes identifying the subject as a low binder of β-glucan, and co-administering to the subject a soluble β-glucan and an antibody preparation capable of converting the subject from a low binder to a high binder.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
C07K 16/14 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from fungi, algae or lichens
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
G01N 33/554 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
Provided herein are methods for treating a viral infection in a patient, comprising administering to said patient a therapeutically effective amount of a PERK inhibitor selected from a compound having the structure (I):
Provided herein are methods for treating a viral infection in a patient, comprising administering to said patient a therapeutically effective amount of a PERK inhibitor selected from a compound having the structure (I).
Provided herein are methods for treating a viral infection in a patient, comprising administering to said patient a therapeutically effective amount of a PERK inhibitor selected from a compound having the structure (I):
The invention relates to methods of using modulators of GCN2 and compositions thereof, in the treatment of cancers and other diseases and disorders associated with GCN2 activation, said modulators having the Formulae I, II, III, IV, V, VI, VII, and/or VIII.
A61K 31/428 - Thiazoles condensed with carbocyclic rings
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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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 31/573 - 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
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula:
2, and W are described herein.
C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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 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 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 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 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
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
Inventor
Bose, Nandita
Beatty, Gregory
Abstract
The present invention relates to the combination of β-glucan and a CD40 agonist for cancer immunotherapy. The combination therapy shows synergistic anti-tumor activity that is dependent on T cells. Surprisingly, the combination therapy is effective against poorly immunogenic tumors.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
36.
Chromenopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula:
where A1, A2, G, R1, R2, R3, R4, and W are described herein.
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
C07D 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
A61K 9/00 - Medicinal preparations characterised by special physical form
Provided herein are compounds of formula (I) as shown below, compositions, and methods useful for inhibiting PERK and for treating related conditions, diseases, and disorders.
Provided herein are compounds of formula (I), compositions, and methods useful for inhibiting PERK and for treating related conditions, diseases, and disorders.
C07D 213/73 - Unsubstituted amino or imino radicals
C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 213/87 - HydrazidesThio or imino analogues thereof in position 3
C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
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 241/28 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
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
Provided herein are compounds of formula (I), compositions, and methods useful for inhibiting PERK and for treating related conditions diseases, and disorders.
Provided herein are compounds of formula (I), compositions, and methods useful for inhibiting PERK and for treating related conditions diseases, and disorders, wherein Q is selected from (Ia), (Ib) ou (Ic).
C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula:
4, and W are described herein.
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
C07D 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
42.
(AZA)INDAZOLYL-ARYL SULFONAMIDE AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS
The invention provides (aza)indazolyl-aryl sulfonamide and related compounds, pharmaceutical compositions, and their use in the treatment of medical conditions, such as cancer, and in inhibiting GCN2 activity.
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 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 403/04 - 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 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 405/12 - 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 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
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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 31/4439 - 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
This disclosure provides, in one aspect, dosing strategies for soluble β-glucan immunotherapy to optimize acute immunopharmacodynamic responses for the immunotherapy and/or subject. It also provides a method for analyzing a sample from a subject for a biomarker to identify the appropriate dosing strategy for soluble β-glucan immunotherapy. Generally, the method includes obtaining a biological sample from a subject, analyzing the sample for a biomarker anti-β-glucan antibody level or immunopharmacodynamic response level, classifying the subject into a subgroup based on the biomarker anti-β-glucan antibody level or immunopharmacodynamic response level and identifying the appropriate dosing strategy based on the subgroup classification.
This disclosure provides, in one aspect, a method for analyzing a sample from a subject for a biomarker that is indicative of the subject's immune response to β-glucan. Generally, the method includes obtaining a biological sample from a subject, analyzing the sample for a biomarker anti-β-glucan antibody compared to a reference standard, computing a Relative Antibody Unit (RAU) value for anti-β-glucan antibody in the sample, and identifying the subject as biomarker positive if the RAU value is greater than a predetermined RAU value for the biomarker anti-β-glucan antibody.
Particulate β-glucan is solubilized at elevated pressure and temperature to form soluble β-glucan. The method is safe and economical and produces a product that is an improved pharmaceutical agent.
The invention generally relates to soluble beta-glucan compositions and method of using such compositions. In one aspect, an adjuvant for a pharmaceutical composition is described which includes a soluble beta-glucan and a TLR agonist, each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen. In another aspect, compositions that generally include an antigen component, a soluble beta-glucan component, and a TLR agonist component and a method that generally includes administering to a subject a composition that comprises a soluble beta-glucan and a TLR agonist, each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen, are described.
This disclosure relates to the combination of soluble β-glucan and immune suppression-relieving agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-angiogenics, checkpoint inhibitors including non-tumor targeting antibodies.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/00 - Medicinal preparations containing antigens or antibodies
48.
Beta-glucan in combination with anti-cancer agents affecting the tumor microenvironment
The present invention relates to the combination of soluble β-glucan and anti-cancer agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-cancer agents.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 39/00 - Medicinal preparations containing antigens or antibodies
49.
Yeast cell wall enriched in mannan oligosaccharide protein
A23L 33/10 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives
A23K 10/16 - Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
A23K 10/38 - Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hayAnimal feeding-stuffs from material of fungal origin, e.g. mushrooms from waste material from distillers' or brewers' waste
This disclosure provides, in one aspect, a method for analyzing a sample from a subject for a biomarker that is indicative of the subject's immune response to β-glucan. Generally, the method includes obtaining a biological sample from a subject, analyzing the sample for a biomarker anti-β-glucan antibody compared to a reference standard, computing a Relative Antibody Unit (RAU) value for anti-β-glucan antibody in the sample, and identifying the subject as biomarker positive if the RAU value is greater than a predetermined RAU value for the biomarker anti-β-glucan antibody.
This disclosure describes, in one aspect, a method for identifying β-glucan binding to immune cells of a subject. Generally, the method includes obtaining a blood sample from the subject, the blood sample comprising immune cells, adding soluble β-glucan to at least a portion of the blood sample and incubating the mixture under conditions allowing the soluble β-glucan to bind to the immune cells, and detecting soluble β-glucan bound to the immune cells. In another aspect, this disclosure describes a method that generally includes identifying the subject as a low binder of β-glucan, and co-administering to the subject a soluble β-glucan and an antibody preparation capable of converting the subject from a low binder to a high binder.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
C07K 16/14 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from fungi, algae or lichens
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
G01N 33/554 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
A61K 39/00 - Medicinal preparations containing antigens or antibodies
52.
Compositions and methods for beta-glucan immunotherapy
This disclosure describes, in one aspect, a composition that includes a β-glucan component and an antibody component that specifically binds to the β-glucan. In another aspect, this disclosure describes a method of increasing a subject's response to β-glucan immunotherapy. Generally, the method includes identifying the subject as a low binder of β-glucan and administering to the subject a composition that comprises a β-glucan moiety conjugated to the therapeutic antibody. In some cases, the therapeutic antibody can be an anti-tumor antibody.
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
C07K 16/14 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from fungi, algae or lichens
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The present invention relates to methods of using neutral soluble glucan and monoclonal antibodies for antitumor therapy. Neutral soluble Beta (1,3; 1,6) glucan (NSG) enhances the tumoricidal activity of the innate immune system by binding to the C3 complement protein receptor CR3. The glucan does not stimulate the induction of inflammatory cytokines. Also described are methods of using whole glucan particles (WGP) as an immunomodulator by inducing a shift from a Th2 response to the Th1 response, leading to an enhanced antitumor cytotoxic T-cell response.
A61K 31/715 - Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkagesDerivatives thereof, e.g. ethers, esters
Described herein are beta-glucan compounds, compositions, and methods. Generally, the methods exploit the observation that beta-glucan compounds can bind to B cells. Thus, the methods generally include administering a beta-glucan compound to a subject in an amount effective for the beta-glucan compound to bind to a B cell and modulate at least one biological function of the B cell.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
The invention generally relates to soluble beta-glucan compositions and method of using such compositions. In one aspect, an adjuvant for a pharmaceutical composition is described which includes a soluble beta-glucan and a TLR agonist, each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen. In another aspect, compositions that generally include an antigen component, a soluble beta-glucan component, and a TLR agonist component and a method that generally includes administering to a subject a composition that comprises a soluble beta-glucan and a TLR agonist, each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen, are described.
Described herein are compositions that include isolated opsonized soluble β-glucan, methods of making those compositions and methods of using those compositions.
C07H 1/00 - Processes for the preparation of sugar derivatives
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 47/61 - 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
Particulate β-glucan is solubilized at elevated pressure and temperature to form particulate-soluble β-glucan. The particulate-soluble β-glucan is capable of being dried to a powder form and subsequently re-solubilized.
Particulate β-glucan is solubilized at elevated pressure and temperature to form particulate-soluble β-glucan. The particulate-soluble β-glucan is capable of being dried to a powder form and subsequently re-solubilized.
Particulate β-glucan is solubilized at elevated pressure and temperature to form particulate-soluble β-glucan. The particulate-soluble β-glucan is capable of being dried to a powder form and subsequently re-solubilized.
Particulate β-glucan is solubilized at elevated pressure and temperature to form soluble β-glucan. The method is safe and economical and produces a product that is an improved pharmaceutical agent.
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 31/496 - 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 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 35/02 - Antineoplastic agents specific for leukemia
62.
PERK INHIBITOR HC-5404 IN COMBINATION WITH ANTI-PD-1 ANTIBODY AND/OR AN ANTIANGIOGENETIC AGENT FOR USE IN THE TREATMENT OF CANCER
Provided herein are methods of treating a cancer (e.g., a solid tumor) in a subject in need thereof. The present disclosure also provides methods of activating the immune system of a subject in need thereof (e.g., a subject having a cancer). The methods described herein generally comprise administering to the subject an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and an immunotherapy (e.g., an anti-PD-1 antibody) and/or an antiangiogenic agent (e.g., VEGFR-TKI).
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
Provided herein are compounds of formula (I), compositions, and methods useful for inhibiting PERK and for treating related conditions, diseases, and disorders.
A61K 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
A61K 31/4433 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
C07D 241/28 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
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 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
Provided herein are compounds of formula (I), compositions, and methods useful for inhibiting PERK and for treating related conditions diseases, and disorders.
This disclosure describes, in one aspect, a method for identifying P-glucan binding to immune cells of a subject. Generally, the method includes obtaining a blood sample from the subject, the blood sample comprising immune cells, adding soluble P-glucan to at least a portion of the blood sample and incubating the mixture under conditions allowing the soluble P-glucan to bind to the immune cells, and detecting soluble P-glucan bound to the immune cells. In another aspect, this disclosure describes a method that generally includes identifying the subject as a low binder of P-glucan, and co-administering to the subject a soluble P-glucan and an antibody preparation capable of converting the subject from a low binder to a high binder.
Provided herein are compounds, compositions, and methods useful for modulating the activity of GCN2 and for treating related conditions, diseases, and disorders (e.g., cancer and neurodegenerative diseases).
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 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
