242 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.

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 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.

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 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 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.

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 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 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.