The present invention relates to use of a compound of Formula (I), Formula (la), Formula (lb), Formula (Ic), Formula (Id), Formula (le), or a pharmaceutically acceptable salt thereof, and a checkpoint inhibitor to treat refractory cancers.
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
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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
A61K 9/00 - Medicinal preparations characterised by special physical form
3.
COMPOSITIONS AND METHODS FOR TREATING CANCER OR PREVENTING, INHIBITING OR REDUCING RISK OF METASTASIS OF A CANCER
STICHTING HET NEDERLANDS KANKER INSTITUUT - ANTONI VAN LEEUWENHOEK ZIEKENHUIS (Netherlands)
Inventor
Kovach, John S.
Bernards, Rene
Dias, Matheus Henrique
Abstract
This invention provides compositions of (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, checkpoint kinase 1 (“CHK1”) inhibitor, B-cell lymphoma-extra large (“BCL-xL”) inhibitor, BCL-xL proteolysis-targeting chimera (“BCL-xL PROTAC”), pan-BCL inhibitor or ataxia telangiectasia and Rad3-related (“ATR”) inhibitor. This invention further provides methods for treating cancer or for preventing, inhibiting, or reducing risk of metastasis of a cancer, such as colorectal cancer, cholangiocarcinoma, pancreatic cancer or ovarian cancer, using (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, CHK1 inhibitor, BCL-xL inhibitor, BCL-xL PROTAC, pan-BCL inhibitor or ATR inhibitor.
STICHTING HET NEDERLANDS KANKER INSTITUUT - ANTONI VAN LEEUWENHOEK ZIEKENHUIS (Netherlands)
Inventor
Kovach, John S.
Bernards, Rene
Dias, Matheus Henrique
Abstract
This invention provides compositions of (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, checkpoint kinase 1 ("CHK1") inhibitor, B-cell lymphoma-extra large ("BCL-xL") inhibitor, BCL-xL proteolysis-targeting chimera ("BCL‑xL PROTAC"), pan-BCL inhibitor or ataxia telangiectasia and Rad3-related ("ATR") inhibitor. This invention further provides methods for treating cancer or for preventing, inhibiting, or reducing risk of metastasis of a cancer, such as colorectal cancer, cholangiocarcinoma, pancreatic cancer or ovarian cancer, using (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, CHK1 inhibitor, BCL-xL inhibitor, BCL‑xL PROTAC, pan-BCL inhibitor or ATR inhibitor.
The present invention provides a method of treating a subject suffering from SCLC comprising administering to the subject an effective amount of a PP2A inhibitor and optionally one or more anti-cancer agents.
A61K 31/4995 - Pyrazines or piperazines forming part of bridged ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
The present invention provides a method of treating a subject suffering from SCLC comprising administering to the subject an effective amount of a PP2A inhibitor and optionally one or more anti-cancer agents.
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
The present invention provides a method of treating a subject suffering from SCLC comprising administering to the subject an effective amount of a PP2A inhibitor and optionally one or more anti-cancer agents.
The present invention provides a method of enhancing the function of CAR T cells comprising administering to the CAR T cells a PP2A inhibitor and optionally one or more anti-cancer therapies.
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
12.
Oxabicycloheptanes for modulation of immune response
The United States of America, as Represented by the Secretary Department of Health and Human Services (USA)
Inventor
Kovach, John S.
Zhuang, Zhengping
Ho, Sze Chun Winson
Wang, Herui
Lu, Rongze
Abstract
The present invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an effective amount of a PP2A inhibitor.
The present invention provides a method of enhancing the function of CAR T cells comprising administering to the CAR T cells a PP2A inhibitor and optionally one or more anti-cancer therapies.
A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
16.
Oxabicycloheptanes and oxabicycloheptenes for the treatment of diabetes
A method of increasing the insulin sensitivity of a mammalian cell by contacting the cell with a protein phosphatase 2A (PP2A) inhibitor having the structure (I).
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
17.
Protein phosphatase 2A inhibitors for treating myelodysplastic syndromes
Disclosed are methods for treating a meylodysplastic syndrome (MDS) in a subject that involves administering to the subject a therapeutically effective amount of a protein phosphatase 2A (PP2A) inhibitor.
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
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
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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 31/706 - 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
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
18.
Oxabicycloheptanes and oxabicycloheptenes, their preparation and use
A method of treating a depressive or stress disorder in a subject afflicted therewith comprising administering to the subject an effective amount of a compound having the structure:
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/343 - 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 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
C07D 303/32 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
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
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
LIXTE BIOTECHNOLOGY, INC. (USA)
Inventor
Kovach, John S.
Zhuang, Zhengping
Ho, Sze Chun Winson
Wang, Herui
Lu, Rongze
Abstract
The present invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an effective amount of a PP2A inhibitor.
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
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Kovach, John S.
Zhuang, Zhengping
Ho, Sze Chun Winson
Wang, Henrui
Abstract
The present invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an effective amount of a PP2A inhibitor.
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
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
23.
Oxabicycloheptanes and oxabicycloheptenes, their preparation and use
Disclosed are methods for treating a myelodysplastic syndrome (MDS) in a subject that involves administering to the subject a therapeutically effective amount of a protein phosphatase 2A (PP2A) inhibitor.
A61K 31/535 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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 31/706 - 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
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
25.
Process of synthesizing 3-(4-methylpiperazine-1-carbonyl)-7-oxabicyclo[2.2.1] heptane-2-carboxylic acid
The present invention provides a process for producing the compound having the structure:
(a) reacting a compound having the structure:
with a compound having the structure:
wherein the first organic solvent is a substituted benzene.
C07D 247/00 - Heterocyclic compounds containing rings having two nitrogen atoms as the only ring hetero atoms, according to more than one of groups
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
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
26.
CLINICAL REGIMEN FOR TREATING MYELODYSPLASTIC SYNDROME WITH PHOSPHATASE INHIBITOR
This invention provides a method of treating myelodysplastic syndrome in a human subject afflicted therewith comprising administering to the subject an amount from 0.1 mg/m2 to 5 mg/m2 of a compound having the structure (I) or a salt, zwitterion, or ester thereof.
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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
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
C07D 307/00 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
A61K 31/343 - 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 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
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
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
30.
Oxabicycloheptanes and oxabicycloheptenes for the treatment of depressive and stress disorders
A method of treating a depressive or stress disorder in a subject afflicted therewith comprising administering to the subject an effective amount of a compound having the structure:
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 303/32 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
A61K 31/343 - 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 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
31.
OXABICYCLOHEPTANES AND OXABICYCLOHEPTENES FOR THE TREATMENT OF DEPRESSIVE AND STRESS DISORDERS
A method of treating a depressive or stress disorder in a subject afflicted therewith comprising administering to the subject an effective amount of a compound having the structure: (I).
A61K 31/343 - 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 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE (France)
Inventor
Kovach, John, S.
Lecca, Salvatore
Mameli, Manuel
Abstract
A method of treating a depressive or stress disorder in a subject afflicted therewith comprising administering to the subject an effective amount of a compound having the structure: (I).
A61K 31/336 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
C07D 303/32 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
33.
PROCESS OF SYNTHESIZING 3-(4-METHYLPIPERAZINE-1-CARBONYL)-7-OXABICYCLO[2.2.1] HEPTANE-2-CARBOXYLIC ACID
The present invention provides a process for producing the compound having the structure: (formula) comprising, (a) reacting a compound having the structure : (formula) with a compound having the structure: (formula) in the presence of a first organic solvent under conditions sufficient to produce the compound, wherein the first organic solvent is a substituted benzene.
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
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
The present invention provides a method of inhibiting protein phosphatase 2A (PP2A) in a human subject in need thereof comprising administering to the subject an amount of from 0.1 mg/m2 to 5 mg/m2 of a compound having the structure (formula I) or a salt, zwitterion, or ester thereof, so as to thereby inhibit protein phosphatase 2A (PP2A) in the subject.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
A61K 9/00 - Medicinal preparations characterised by special physical form
36.
PROTEIN PHOSPHATASE 2A INHIBITORS FOR TREATING MYELODYSPLASTIC SYNDROMES
H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC. (USA)
LIXTE BIOTECHNOLOGY INC. (USA)
Inventor
List, Alan F.
Sallman, David A.
Kovach, John S.
Abstract
Disclosed are methods for treating a meylodysplastic syndrome (MDS) in a subject that involves administering to the subject a therapeutically effective amount of a protein phosphatase 2A (PP2A) inhibitor.
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
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 UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)
Inventor
Kovach, John, S.
Zhuang, Zhengping
Chang, Ki-Eun
Hall, Matthew
Gottesman, Michael, M.
Abstract
A method of treating ovarian cancer in a subject afflicted therewith comprising administering to the subject an effective amount of an anti-cancer agent and an effective amount of a compound having the structure:
A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
A method of increasing the insulin sensitivity of a mammalian cell by contacting the cell with a protein phosphatase 2A (PP2A) inhibitor having the structure:
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
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
39.
PROTEIN PHOSPHATASE INHIBITORS THAT CROSS THE BLOOD BRAIN BARRIER
The present invention provides a method for in vivo delivery of endothal to a target cell in a subject, the method comprising administering to the subject a compound having the structure: Formula (I).
AbstractThe invention relates to a pharmaceutical composition, methods of preparing the same, and a sealed package comprising said pharmaceutical composition, the pharmaceutical composition comprising a protein phosphatase 2A (PP2A) inhibitor of the general formula 3-(4methylpiperazine-carbony1)-7-oxalobicyclo[2.2.1]heptane-2-carboxylic acid, a zwitterion, an enantiomer, or salt thereof and monosodium glutamate, suitable for the administration to human subjects afflicted with a condition or disease amenable to treatment with a PP2A inhibitor, such as cancer, a neurodegenerative disease, a loss of protein function caused by a genetic abnormality associated with such condition or disease. The invention also provides methods of reducing reperfusion injury, tissue damage associated with reperfusion injury, vascular leakage associated with reperfusion injury, tissue damage due to an acute trauma, and vascular leakage due to an acute trauma, comprising administering a therapeutically effective amount of the pharmaceutical composition of the invention to a subject in need thereof.R1 R2R7 \ /CNR31: a 0R4/CR8 / IR6R6Date Recue/Date Received 2020-10-14
A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
A61K 31/343 - 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 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
42.
FORMULATIONS OF OXABICYCLOHEPTANES AND OXABICYCLOHEPTENES
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
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
43.
SANGUINARINE ANALOG PP2C INHIBITORS FOR CANCER TREATMENT
A61K 31/435 - 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
A61K 31/4355 - 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 oxygen as a ring hetero atom
A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
44.
HDAC INHIBITORS FOR TREATING TRAUMATIC BRAIN INJURY
The present inventions provides a method of treating a subject suffering from traumatic brain injury comprising administering to the subject an effective amount of an HDAC inhibitor, structurally represented, thereby treating the subject suffering from traumatic brain injury.
A01N 43/40 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
A method of increasing the insulin sensitivity of a mammalian cell by contacting the cell with a protein phosphatase 2A (PP2A) inhibitor having the structure (I).
A method of reducing reperfusion injury in mammalian tissue comprising contacting the tissue with a protein phosphatase 2A (PP2A) inhibitor having the structure.
THE U.S.A., AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Kovach, John, S.
Zhuang, Zhengping
Lu, Jie
Yang, Chunzhang
Lonser, Russell
Abstract
A method of treating a mammalian subject afflicted with a disease characterized by a loss of protein function caused by a genetic abnormality associated with the disease comprising administering to the subject a therapeutically effective amount of a protein phosphatase 2A inhibitor or a histone deacetylase inhibitor.
A61K 31/4468 - Non-condensed piperidines, e.g. piperocaine having a nitrogen atom directly attached in position 4, e.g. clebopride, fentanyl
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
50.
Oxabicycloheptanes and oxabicycloheptenes, their preparation and use
C07C 233/65 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
Disclosed herein are methods of treating neurodegenerative diseases comprising administering to the subject a compound having the structure:
8 are described herein, or a compound having the structure:
33 are described herein.
Disclosed herein are methods of inhibiting the function of p53 in a cell by contacting the cell with an effective amount of a PP2A inhibitor. Also disclosed herein are processes for producing an induced pluripotent stem (iPS) cell by contacting a somatic cell expressing at least one gene that encodes a reprogramming factor with an amount of a PP2A inhibitor effective to produce the iPS cell; reversibly inhibiting p53 function during production of an iPS cell by contacting a somatic cell with an amount of a PP2A inhibitor effective to reversibly inhibit p53 function; increasing the likelihood of producing an (iPS) cell.
A01N 43/42 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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
55.
Neuroprotective agents for the prevention and treatment of neurodegenerative diseases
Disclosed herein are methods of treating neurodegenerative diseases comprising administering to the subject a compound having the structure:
8 are described herein, or a compound having the structure:
33 are described herein.
A61K 31/54 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame
THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Kovach, Johh S.
Zhuang, Zhengping
Lu, Jie
Abstract
Disclosed herein are methods of inhibiting proliferation of a cancer cell or inducing apoptosis of a cancer cell, which does not overexpress N-CoR. Also disclosed herein are methods of inhibiting proliferation or inducing apoptosis of a cancer cell that overexpresses TCTP and methods for determining whether a compound is effective in inducing cell death.
A01N 43/00 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
57.
NEUROPROTECTIVE AGENTS FOR THE PREVENTION AND TREATMENT OF NEURODEGENERATIVE DISEASES
Disclosed herein are methods of treating neurodegenerative diseases comprising administering to the subject a compound having the structure: ( l ) wherein α and R1-R8 are described herein, or a compound having the structure: ( ll ) wherein Y, Z, and R21, R24 / R25, and R31 -R33 are described herein.
C07C 233/65 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
This invention provides the compound having the structure wherein n is 1- 10; X is C-R11 or N, wherein R11 is H, OH, SH, F, Cl, SO2R7, NO2, trifluoromethyl, methoxy, or CO-R7, wherein R7 is alkyl, alkenyl, alkynyl, C3-C8 cycloalkyl, or aryl; R2 is H or NR3R4, wherein R3 and R4 are each independently H, C1-C6 alkyl, or C3-C8 cycloalkyl; R5 is OH or SH; and R6, RI2A RI3, and R14 are each independently H, OH, SH, F, CI, SO2R15, NO2, trifluoromethyl, methoxy, or CO-R15, wherein R15 is alkyl, alkenyl, alkynyl, C3-C8 cycloalkyl, or aryl, or a salt of the compound, which is useful in the treatment of tumors.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Kovach, John, S.
Zhuang, Zhengping
Abstract
Disclosed herein are methods of treating neuroblastomas and medulloblastomas in a subject comprising administering to the subject a phosphatase ligand in an amount effective to treat the subject. Also disclosed herein are method of treating neuroblastomas and medulloblastomas in a subject comprising administering to the subject a histone deacteylase ligand in an amount effective to treat the subject.
A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
patents
