48 results about "PARP1" patented technology

Provided are a process for preparing a Parp1 / 2 inhibitor, i.e., (R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one (hereinafter referred to as Compound A), crystalline forms (poly-morphs) of Compound A or hydrate or solvate thereof, methods for preparing the crystalline forms, and the use thereof.

Compounds that are not related to NAD, and which target PARP1-histone H4 interaction are provided, as well as compositions of these compounds, and methods for specific inhibition of poly(ADP-ribose) polymerase 1 (PARP-1) using these compounds are provided. These PARP-1 inhibitors may be used to treat cancer in which PARP-1 activation or biologic activity plays a role, including prostate cancer, breast cancer, kidney cancer, ovarian cancer, lymphoma, leukemia, and glioblastoma, among others.

In one embodiment, the invention provides a method of treating a subject suffering from a breast cancer tumor which is non-responsive or intrinsically resistant to anti-estrogen therapy comprising administering a therapeutically effective amount of an inhibitor of alternative (ALT) non-homologous end joining (NHEJ) factor to the subject.In another embodiment the invention provides a method of treating a subject who suffers from a pancreatic cancer which is non-responsive to chemotherapy and / or radiation comprising co-administering a therapeutically effective amount of PARP1 inhibitor and a DNA ligase IIIα inhibitor to the subject. Related diagnostic methods, nucleic acid arrays, devices and kits are also provided.

The invention relates to the field of biomedicine, and discloses the application of PARP1 inhibitors in the preparation of tumor immunotherapy preparations. The invention finds that PARP1 inhibitors can enhance the efficacy of tumor immunotherapy and reduce toxic and side effects. Specifically: (1) PARP1 inhibitors can reduce the virus clearance ability and increase the duration of oncolytic virus on tumor cells, thereby improving the anti-tumor ability of oncolytic virus. (2) PARP1 inhibition can significantly reduce the cytokines and chemokines released by macrophages, and reduce the immune cytokine storm induced by oncolytic virus, thereby reducing the toxic side effects of oncolytic virus in tumor immunotherapy. The present invention has far-reaching significance for tumor immunotherapy.

The invention discloses application of a PARP1 inhibitor in the preparation of a medicine for reversing drug resistance of tumor cells to amethopterin and belongs to the technical field of tumour biotherapy. It is found by the inventor through researches that as for malignant cells with MTX resistance and DHFR gene high-amplification, by specifically inhibiting the key protein RARP1 of A-NHEJ pathway, DHFR gene copy number can be reduce and DMs in cells can be decreased so as to reverse drug resistance of tumors and enhance efficiency of tumor therapy. Therefore, on the basis of the above researches, the invention brings forward the application of the PARP1 inhibitor in the preparation of a medicine for reversing the drug resistance of tumor cells to MTX by reducing DHFR gene copy number. The invention provides a new targeting therapeutic scheme for the MTX as the main therapeutic drug and for the biotherapy of malignant tumors which are easy to resist drugs and also provides a scientific basis for effectively fighting against MTX drug resistance. In addition, the invention is also of great positive significance for deeply understanding the nature of chemotherapy resistance and finding resistance target for individualized treatment.

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2 / - / -isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and / or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.

The invention relates to an application of 3-[3-[[[2-chloro-3-(trifluoromethyl) phenyl] methyl] (2,2-xenylethyl) amino] propoxy] phenylacetate (abbreviated as GW3965) as 1-type poly (ADP-ribose) synthetase inhibitor. GW3965 is an LXR agonist, and has no cytotoxic effects of common anti-tumor drugs or other 1-type poly (ADP-ribose) synthetase inhibitors as the cholesterol analogue, and the safety of GW3965 can be predicated. GW3965 can be widely applied as the medicine for treating cholesterol related diseases, including cardiovascular diseases, tumour and the like.