247 results about "PARP inhibitor" patented technology

The present invention provides a compound of Formula (I):wherein the variables Z, n, Y and p are as defined herein, and pharmaceutically acceptable salts thereof, which can inhibit the activity of poly (ADP-ribose)polymerases, and pharmaceutical compositions comprising the same.

The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and / or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and / or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and / or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and / or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators.

In one aspect, the present invention provides a method of treating uterine cancer, endometrial cancer, or ovarian cancer, comprising administering to a subject at least one PARP inhibitor. In another aspect, the present invention provides a method of treating uterine cancer, endometrial cancer, or ovarian cancer, comprising administering to a subject at least one PARP inhibitor in combination with at least one anti-tumor agent.

The present invention relates to a computer-assisted method of a designing of a PARP inhibitor comprising: a) determining an interaction between a candidate PARP protein and a known PARP inhibitor by evaluating a binding of the PARP protein to the known PARP inhibitor; b) based on the interaction, designing a candidate PARP inhibitor; c) determining an interaction between the PARP protein and the candidate PARP inhibitor by evaluating a binding of the PARP protein to the candidate PARP inhibitor; and d) concluding that the candidate PARP inhibitor inhibits the PARP protein wherein the conclusion is based on the interaction of step c). The invention also provides methods for treatment of diseases with the candidate PARP inhibitors.

The present invention relates to a method of treating a fatty acid synthesis related disease comprising administering to a patient in need thereof an effective amount of a PARP inhibitor or metabolite thereof to inhibit fatty acid synthesis, wherein the fatty acid synthesis related disease is obesity, diabetes, or cardiovascular disease. The present invention also relates to a method of treating a cancer in a subject comprising: (i) identifying a level of fatty acid in a sample from the subject, and (ii) administering an effective amount of a PARP inhibitor or metabolite thereof to inhibit fatty acid synthesis in the subject, wherein the administration is based on the level of fatty acid, thereby treating the cancer in the subject. The present invention further relates to a method of treating Her-2 related cancers by administering to a patient in need thereof an effective amount of a PARP inhibitor or metabolite thereof to inhibit fatty acid synthesis.

The present invention provides compounds comprising a bicyclic aryl moiety, such as 2H-phthalazin-1-one or derivatives thereof, compositions comprising the same, and methods for producing and using the same. In particular, the present invention provides compounds of the formula: or a pharmaceutically acceptable salt, a hydrate, a solvate, or a prodrug thereof; where Q1, Q2 and Y are those defined herein.

A compound represented by: or a salt thereof, and a pharmaceutical composition containing the compound or the salt, the compound having a poly (ADP-ribose)polymerase inhibitory effect, and is safe and advantageous for drug formulation.

The present invention relates to methods of identifying a disease treatable with PARP modulators by identifying a level of PARP in a sample of a subject, making a decision regarding identifying the disease treatable by the PARP modulators wherein the decision is made based on the level of PARP. The method further comprises of treating the disease in the subject with the PARP modulators. The methods relate to identifying up-regulated PARP in a disease and making a decision regarding the treatment of the disease with PARP inhibitors. The extent of PARP up-regulation in a disease can also help in determining the efficacy of the treatment with PARP inhibitors. The present invention discloses various diseases that have up-regulated or down-regulated PARP and can be treated with PARP inhibitors or PARP activators, respectively. The examples of the diseases include cancer, inflammation, metabolic disease, CVS disease, CNS disease, disorder of hematolymphoid system, disorder of endocrine and neuroendocrine, disorder of urinary tract, disorder of respiratory system, disorder of female reproductive system, and disorder of male reproductive system.

A compound of the formula (I): wherein ring A is a carbocyclic group, R1 is hydrogen or a halogen atom or a lower alkyl group, R2 is a di(lower)alkylamino group or N-containing heterocyclic group, among which the N-containing heterocyclic group may be substituted with one or more substituent(s), Y is an oxygen or sulfur atom, n is an integer from 0 to 2, and m is an integer from 0 to 4, or its prodrug, or their salt which has poly(adenosine 5′-diphospho-ribose)polymerase inhibiting activity.

The invention discloses a method for predicating a homologous recombination deficiency (HRD) mechanism and a method for predicating response of patients to cancer therapy and relates to the field of biological information predication. The method comprises the step of judging whether a tumor sample has homologous recombination deficiency or not according to one or more comprehensive values in a large-segment INDEL (Insertion / Deletion) fraction, a copy number variation fraction and a tumor mutation load fraction, wherein the comprehensive values can also comprise a loss of heterozygosity variation fraction. By adopting the method disclosed by the invention, predication of a chromosome large-segment structure, a chromosome gene type number, a chromosome gene copy number, a chromosome variation interval and abnormal loss of heterozygosity and chromosome telomeric imbalance is realized, so that an evaluation range is more complete and HRD can be accurately predicated; the comprehensive values also can be used for determining whether the patients have response to a therapeutic regimen containing one or more of a PARP (Poly Adenosine Diphosphate Ribose Polymerase) inhibitor, an DNA (Deoxyribonucleic Acid) injury inhibitor, a topoisomerase II / II+inhibitor, a topoisomerase I inhibitor and radiotherapy; the method is simple and has wide general applicability.

In one aspect, the present invention provides a method of treating breast cancer that is negative for at least one of ER, PR, or HER2, comprising administering to a subject at least one PARP inhibitor. In another aspect, the present invention provides a method of treating breast cancer comprising administering to a subject at least one PARP inhibitor in combination with at least one anti-tumor agent.

The present invention relates to tetraaza phenalen-3-one compounds which inhibit poly (ADP-ribose) polymerase (PARP) and are useful in the chemosensitization of cancer therapeutics. The induction of peripheral neuropathy is a common side-effect of many of the conventional and newer chemotherapies. The present invention further provides means to reliably prevent or cure chemotherapy-induced neuropathy. The invention also relates to the use of the disclosed PARP inhibitor compounds in enhancing the efficacy of chemotherapeutic agents such as temozolomide. The invention also relates to the use of the disclosed PARP inhibitor compounds to radiosensitize tumor cells to ionizing radiation. The invention also relates to the use of the disclosed PARP inhibitor compounds for treatment of cancers with DNA repair defects.

The present invention provides novel phthalazinone compounds and isomer thereof, pharmaceutically acceptable salts, solvates, chemically protected forms, and prodrugs; which can be used as PARP inhibitor and pharmaceutical compositions containing the novel phthalazinone compounds; wherein A, R1 and X are defined as shown. The medicine is used for the treatment of: vascular diseases, neurotoxicity, or diseases improved through the inhibition of PARP activity; or used as adjuvants for the treatment of cancers, or used for enhancing the therapeutic effect of radiation or chemotherapeutic agents on tumor cells, wherein the cancers includes breast cancer, ovarian cancer, colon cancer, melanoma, lung cancer, gastrointestinal stromal tumor, brain cancer, cervical cancer, pancreatic cancer, prostate cancer, gastric cancer, chronic myeloid leukocytes hypercytosis, liver canser, lymphoma, peritoneal cancer, soft tissue sarcoma, neuroendocrine tumors, advanced solid tumors, and glioblastoma.

The present invention relates to methods of identifying a disease treatable with PARP modulators by identifying a level of PARP in a plurality of samples from a population, making a decision regarding identifying the disease treatable by the PARP modulators wherein the decision is made based on the level of PARP. The method further comprises of treating the disease in a subject population with the PARP modulators. The methods relate to identifying up-regulated PARP in a disease and making a decision regarding the treatment of the disease with PARP inhibitors. The extent of PARP up-regulation in a disease can also help in determining the efficacy of the treatment with PARP inhibitors.The present invention discloses various diseases that have up-regulated or down-regulated PARP and can be treated with PARP inhibitors or PARP activators, respectively. The examples of the diseases include cancer, inflammation, metabolic disease, CVS disease, CNS disease, disorder of hematolymphoid system, disorder of endocrine and neuroendocrine, disorder of urinary tract, disorder of respiratory system, disorder of female reproductive system, and disorder of male reproductive system.

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, more preferably 8 or 10 mg / kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

In one aspect, the present invention provides a method of treating breast cancer that is negative for at least one of ER, PR, or HER2, comprising administering to a subject at least one PARP inhibitor. In another aspect, the present invention provides a method of treating breast cancer comprising administering to a subject at least one PARP inhibitor in combination with at least one anti-tumor agent.

The present invention provides compositions of matter, kits and methods for their use in the treatment of cancer. In particular, the invention provides compositions and methods for treating cancer in a subject by inhibiting a poly-ADP-ribose polymerase, as well as providing formulations and modes of administering such compositions.

Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.

The invention provides a novel synthesis method for preparing a PARP inhibitor Niraparib. The method comprises the steps that a starting material methyl anthranilate is subjected to diazo coupling, cyclization, amidation, BOC removal and chiral resolution, and then the Niraparib with the purity reaching 99.5% is obtained. The method is simple, convenient and easy to operate suitable for industrial production.

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, more preferably 8 or 10 mg / kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

The invention provides pharmaceutical formulations of inhibitors for poly (ADP-ribose) polymerase (PARP) enzyme. The formulations can be used in the treatment and prevention of cancer as well as the treatment of neurotrauma and neurodegenerative diseases. The PARP inhibitor is delivered in the form of nanoparticles that provide efficient delivery of the inhibitor into cancer cells or other cells and release of the inhibitor within the cells. In treating cancer, the result is killing of tumor cells, whereas in treatment of neurotrauma and neurodegenerative disease, the result is preservation of cell function.

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg / kg and 18 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg, more preferably 8 or 10 mg / kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

The present invention relates to a method of treating cancer using PARP inhibitors as radio-sensitization agents of tumors. Specifically the present invention relates to a method of radio-sensitization of tumors using a compound of Formula (I)or a pharmaceutically acceptable salt form thereof. The present invention also relates to a pharmaceutical compositions of PARP inhibitors for radiosensitizing tumors.

The invention discloses a series of 4H-pyrazolo[1,5-[alpha]]benzimidazole compound analogues as a PARP inhibitor and particularly discloses the compound represented as the formula (I) as the PARP inhibitor or pharmaceutically acceptable salts thereof.

The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase cellular NAD+ levels and enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a mitochondrial uncoupler or / and a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, metabolic disorders, and other disorders and conditions.

The invention relates to a novel 2-phenyl-1H-benzimidazole-4-formic ether PARP (Poly(ADP-Ribose)Polymerase) inhibiting agent (shown as a formula I), and discloses a preparation method of a compound and medical application thereof. The compound can be used for preparing anticancer medicaments, anti-ischemia-reperfusion injury medicaments, anti-inflammation medicaments, anti-degenerative disease injury medicaments and all treatment medicaments for diseases of which the PARP-1 / 2 inhibiting activities can be improved.

Methods and systems for identifying a cancer patient suitable for treatment with a PARP inhibitor. A 6-gene, 7-gene and 8-gene predictor panels of genes that are predictive of patient resistance or sensitivity to PARP inhibitors such as Olaparib.

The present invention relates to combination therapy with ADCs against a tumor-associated antigen, such as Trop-2, and drugs, such as microtubule inhibitors and / or PARP inhibitors. Where ADCs are used, they preferably incorporate SN-38 or another drug that induces DNA strand breaks. Preferably, the combination of ADC and PARPi or microtubule inhibitor exhibits synergistic effects against the cancer. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.