48 results about "PARP1" patented technology

The invention discloses an anti-aging composition for improving co-enzyme I, a preparation and a preparation method thereof. The anti-aging composition is prepared from the following raw materials andcomponents in parts by weight: 0.005 to 0.02 part of methylpyridine chromium, 0.05 to 0.2 part of folic acid, 100 to 250 parts of quercetin, 30 to 80 parts of resveratrol, 10 to 100 parts of niacinamide, 10 to 300 parts of niacin, 10 to 50 parts of soluble magnesium, and 300 to 600 parts of leucine. The anti-aging composition and the preparation have the advantages that the content of the coenzyme I (NAD) in cells is effectively increased; by compounding with other natural components, the histone deacetylase family (SIRT 1-7) for cell growth, metabolism and survival can be more effectively activated, the health of mitochondria is maintained, the energy metabolism of the cells is optimized, the activity of the gene repair enzyme PARP1 is maintained, the injury of the cells is restored, thegeneration of the cells is enhanced, and the functions of a human body are regulated and optimized; a user can reach the purposes of more effectively resisting aging, and reducing deteriorative disease risk of the patient.

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 invention relates to a kit for predicting colorectal cancer liver metastases and a use method. The kit includes a DNA database building kit, the DNA database building kit comprises probes of a plurality of genes, and the plurality of genes include: high risk genes: KRAS, BRAF, MLH1, NRAS, MSH2, PMS2, UGT1A1, MSH6 AKT1, PIK3CA, PTEN, SMAD4, TP53, NM23, TIAM1, MTS1; and low risk genes: PRKDC, RAD50, STAG2, XRCC5, XRCC6, FANCA, ATR, MUTYH, EMSY, ERCC4, RAD51, PARP1, XRCC1. The kit provided by the invention performs related mutation detection on colorectal cancer liver metastases related genes in peripheral blood, and combines specific scoring mechanism to rapidly and conveniently judge and predict colorectal cancer liver metastases.

The invention discloses an agent box for detecting idiogenetics gene repair capacity. The agent box comprises specificity primer pair and specificity fluorescent detecting probe pair for detecting synchronously number rs1136410 SNP site on multi-poly ADP ribose transferase gene (PARP1), number rs1799782 and rs25487 SNP site on human beings X ray intervein complementation repair gene (XRCC1), number rs1799793 and rs13181 on cutting repair complexes gene (ERCC2), general component for detecting fluorescent definite quantity PCR etc.. The agent box of the invention assesses idiogenetics gene repair capacity by detecting synchronously mononucleotide polymorphism site gene type correlative closely to idiogenetics gene repair capacity.

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 provides a polypeptide for antagonizing the ribonucleic acid (RNA) binding activity of a protein PARP1, and application of the polypeptide. The amino acid sequence of the polypeptide is as shown in SEQ ID No.1; the invention also relates to an anti-tumor polypeptide and application thereof; the anti-tumor polypeptide comprises a tumor cell kill structure domain and a transmembrane structure domain, and the amino acid sequence of the tumor cell kill structure domain is as shown in SEQ ID No.1. The transmembrane structure domain of the anti-tumor polypeptide per se does not have cytotoxicity, but has obvious effects of inhibiting tumor proliferation and migration attack after being connected with the tumor cell kill structure domain. The anti-tumor polypeptide provided by the invention not only can be used as an anti-tumor biological treatment drug alone, but also is expected to be combined with other treatment ways for inhibiting tumors.

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.

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.

The invention provides a combination medicine for treating cancer, and belongs to the technical field of medicines. The combination medicine comprises a PARP1 inhibitor and an FOXM1 inhibitor. The two inhibitors have the limitations of narrow indications, easiness in drug resistance and the like when independently used for treating tumors. The medicine composition provided by the invention can obtain a very strong anti-tumor effect according to an effective administration dosage and an administration mode, and shows a relatively good synergistic effect. Particularly, the medicine composition provided by the invention shows a stronger effect than a single medicine in inhibiting the growth of tumors such as triple-negative breast cancer and pancreatic cancer, and provides a new way for tumor treatment.

The present invention discloses a reagent kit which detects the genetic susceptibility of the synthetic disease of adult woman. The reagent kit comprises a specific primer pair and a specific fluorescent probe pairs which simultaneously detects the SNP polymorphic genotype on the genes of CYBA, CAT, LPL, LEP, ADIPOQ, SOD3, IL3, NOS3, CTLA4, ENOS, ESR2, ERCC1, MTHFR, MS4A2, XRCC1, ALDH2, TNFA, MTR, CCL5, COMT, GSTP1, PPARG, PARP1, OPG, VDR, PON1, ABCA1, MTRR, ERCC2, AT1R, AGT, CCND1, UCP2, ADH2, ADBR2, APOB, CYP11B2, CYP1A1, CYP2E1, CETP, NQO1, IL6, CYP2A13, CBS, a routine component which is used for the fluorescent quantitative PCR testing and the like. The reagent kit of the invention evaluates the genetic susceptibility of the synthetic disease of adult woman through simultaneously detecting the mononucleotide polymorphism site genotype which is closely linked to the genetic susceptibility of the synthetic disease of adult woman.

The present invention provides a kit for detecting genetic predisposition of adult male syndrome. The kit includes specific primer pairs and specific fluorescent probe pairs for detecting 48 SNP polymorphism genotypes on the genes LPL, TNF-alpha, LEP, ADIPOQ, SOD3, IL3, CTLA4, ENOS, ESR2, ERCC1, MTHFR, MS4A2, XRCC1, ALDH2, TNFA, MTR, CCL5, COMT, GSTP1, PPARG, PARP1, OPG, VDR, PON1, ABCA1, MTRR, ERCC2, AT1R, AGT, CCND1, UCP2, ADH2, ADBR2, APOB, CYP11B2, CYP1A1, CYP2E1, CETP, NQO1, IL6, CYP2A13 at the same time, and normal components for FQ-PCR detection. The kit of the invention evaluates the genetic predisposition of adult male syndrome by detecting the genotypes of the 48 SNP polymorphism sites at the same time which is tightly relative to the genetic predisposition of adult male syndrome.

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 present invention relates to methods of treating a condition associated with mTORC1 hyperactivation or TSC2-deficient cancer, the method comprising administering to a subject having the cancer a pharmaceutically-effective amount of a poly(ADP-ribose) polymerase 1 (PARP1) inhibitor. In some embodiments, the condition associated with mTORC1 hyperactivation is tuberous sclerosis complex (TSC). In some embodiments, the condition associated with mTORC1 hyperactivation is lymphangioleiomyomatosis (LAM). In some embodiments, the condition associated with mTORC1 hyperactivation is TSC2-deficient cancer.

Provided herein are methods for identifying and treating cancers that are resistant to PARP inhibition. Methods for sensitizing cancers to a PARP inhibitor therapy are also provided. In some aspects. PARP inhibitor cancers are treated with a PARP inhibitor therapy in combination with a c-Met inhibitor therapy.

The invention belongs to the field of medicinal chemistry, and particularly relates to a preparation method of a terminal anchor polymerase inhibitor with a structure shown in a formula I. The prepared compound has certain inhibitory activity against both PARP1 and PARP2.