59 results about "PARP1" patented technology

The application relates to the technical field of biological medicine, and discloses a micropeptide miPEP060 coded by a LINC00060 gene and application thereof; the application provides the following application of LINC00060 and the micropeptide miPEP060 coded thereby: preparing a product for predicting tumor chemotherapy efficacy, preparing a product for predicting tumor prognosis; preparing a tumor treatment product, preparing a product for enhancing tumor chemotherapy efficacy, preparing a product for overcoming tumor chemotherapy drug resistance, preparing a product for inhibiting PARP1 enzyme activity or PARylation modification, and preparing a product for inhibiting replication stress response and replication fork stability; the LINC00060 and the micropeptide miPEP060 coded thereby provided by the application can significantly enhance the chemotherapy killing effect of tumor cells or tumor tissues and reduce tumor volume.

Disclosed in the present invention are a PARP1 / CDK6 dual-target inhibitor, and a preparation method therefor and the use thereof. The PARP1 / CDK6 dual-target inhibitor is a compound having a structure represented by formula I, or a pharmaceutically acceptable salt or solvate thereof, wherein L is selected from or , and R is selected from the group consisting of hydrogen, deuterium, halogen, hydroxyl, sulfhydryl, cyano, nitro, methoxy, a C1-C8 alkyl, or a C3-C8 cycloalkyl. The PARP1 / CDK6 dual-target inhibitor of the present invention exhibits good effects against human breast cancer cells, and maintains a good in vitro enzyme inhibitory activity against CDK6 and PARP1. Disclosed in the present invention is the use of a CDK6 / BRD4 dual-target inhibitor in the preparation of a drug for treating PARP1 / CDK6-mediated diseases. Disclosed in the present invention is the use of a PARP1 / CDK6 dual-target inhibitor in the preparation of a drug for treating or preventing triple-negative breast cancer.

The invention discloses a PARP1 inhibitor with methyl-1 'H-spiro [piperidine-4, 2'-quinazoline]-4 '(3' H)-ketone as a mother nucleus and a preparation method and application of the PARP1 inhibitor, a main compound has good PARP1 inhibitory activity (IC50 is at a submicromole level), and compared with a PARP1 inhibitor olaparib on the market, the compound has better anti-myocardial hypertrophy activity, and can be used for preparing a medicine for treating myocardial hypertrophy. The potential of PARP1 as a target spot for treating cardiac hypertrophy is proved, and a potential therapeutic drug is provided for treating cardiac hypertrophy.

The invention relates to the field of medicines, in particular to application of tRF-5030c in preparation of a product for treating non-small cell lung cancer. The tRF-5030c provided by the invention is not a simple sequence design product, but is a direct experimental evidence based on the interaction of the tRF-5030c and the double-target protein. Cooperative regulation and control of two key mechanisms are achieved through the single molecular entity, and the problems of low synergistic efficiency and toxicity superposition caused by pharmacokinetic differences, structural isomerism and action target cell heterogeneity of multiple drugs are fundamentally solved. It is ensured that dual inhibition of PARP1 mediated DNA repair and EGFR driven survival signals is highly consistent in time and space.

The present invention relates to a tricyclic compound of formula (I) and its analogue useful for the treatment of breast and ovarian cancer. In particular, the present invention relates to novel tricyclic compound as PARP1 / 2 inhibitor, designed to block the activity of the enzyme Poly (ADP-ribose) polymerase (PARP1 / 2), which plays a crucial role in DNA damage repair, particularly in cancer cells. The synthesized inhibitor molecules having improved solubility, bioavailability and no haematological toxicity can be useful in potential cancer therapies, and defects in DNA repair pathways.

The PARP1 inhibitor compound has a structure of formula (I), wherein R1 and R4 are independently selected from H and organic groups. R2 and R3 are independently absent and are H or an organic group. Z1 and Z2 are independently C or N. L has a structure as shown in a formula (II). Each X1 is independently selected from C and N. Each X2 is independently selected from the group consisting of C, N, O, and S. N, m, p, q, r, and s are each in the range of 0 to 6. M + n, p + q, and r + s each range from 2 to 6. Each R5A, R5B, R5C and R6 is independently absent, is H or an organic group. Qa, Qb, and Qc are each independently a bond or an organic linker. The compounds are useful in pharmaceuticals, for example in the treatment of cancer. Compositions and kits comprising the compounds as well as methods of synthesizing the compounds are also provided.

The present disclosure relates to therapeutic combinations of PARP1 targeting agents with radiation therapy and methods of using the same.

To provide a PARP1 inhibitor and its use.SOLUTION: PARP1 inhibitors and pharmaceutical compositions comprising such inhibitors are described herein. The subject compounds and compositions are useful for the treatment of cancer. The compounds described herein are administered to a subject in need thereof according to standard pharmaceutical practice, either alone or in combination with pharmaceutically acceptable carriers, excipients or diluents, in a pharmaceutical composition. In one embodiment, the compounds of the invention can be administered to an animal. The compounds can be administered orally or parenterally, including the intravenous, intramuscular, intraperitoneal, subcutaneous, rectal and topical routes of administration.SELECTED DRAWING: None

The present invention relates to a FOX protein serving as a PARP1 inhibitor in DNA repair. A novel interaction mechanism between the FOX protein and PARP1 was identified, and the FOX protein was found to act as a direct regulator in a DNA damage repair process. A 12AA-helix3 peptide consisting of 12 amino acids according to the present invention can improve DNA repair efficiency by promoting a homologous recombination repair pathway. Therefore, the present invention can be effectively applied to the development of: a novel DNA repair promoter based on the FOX protein-PARP1 interaction; and a composition for treating cancer.

The application discloses a kind of lactam compounds and purposes thereof, and belongs to the technical field of chemical medicine.The lactam compound provided in the application can be used as a PARP1 inhibitor, has the advantages of high activity and high selectivity, and also has excellent pharmacokinetic properties, excellent safety and potential for brain penetration.

The invention provides a benzenesulfonamide derivative, a preparation method thereof and application of the benzenesulfonamide derivative in preparation of PARP1 inhibitors and antitumor drugs, and belongs to the technical field of medicines. The invention synthesizes a novel benzenesulfonamide derivative, namely a compound N, 4-dimethyl-N-(7H-pyrrolo [2, 3-d] pyrimidine-4-yl) benzenesulfonamide, and the benzenesulfonamide derivative provided by the invention can inhibit PARP1 enzyme activity in a targeted manner so as to inhibit DNA repair, activate a p53-mediated DDR signal channel, inhibit DNA repair and inhibit the expression of a p53-mediated DDR signal channel. The benzenesulfonamide derivative can induce apoptosis of lung cancer tumor cells and influence the cycle of the lung cancer tumor cells, has remarkable antitumor activity, and is simple in synthesis method, easy in raw material obtaining, high in synthesis route yield, environment-friendly and simple and convenient in operation process. The PARP1 inhibitor disclosed by the invention is simple in preparation process, high in drug purity, high in yield, stable in quality and easy for large-scale production. The compound disclosed by the invention has a wide prospect in the aspects of development and application of antitumor drugs.

This article describes PARP1 inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions may be used to treat cancer.

The present invention relates to fused tricyclic PARP1 inhibitors, their preparation methods, and uses. Specifically, the present invention relates to compounds that inhibit poly(ADP-ribose) polymerase activity, pharmaceutical compositions thereof, and uses thereof. The present invention particularly relates to compounds of formula (I), pharmaceutical compositions containing these compounds, and the use of these compounds in the preparation of medicaments for preventing and / or treating diseases, particularly diseases ameliorated by inhibition of PARP1. [Formula 1] TIFF2025538192000118.tif42170

A pharmaceutical product is provided for the administration of an anti-HER2 antibody-drug conjugate in combination with a PARP1 selective inhibitor. The anti-HER2 antibody-drug conjugate has the following formula: [Formula 1] JPEG2023545096000101.jpg78170 wherein A represents the attachment position to the antibody, is conjugated to the anti-HER2 antibody via a thioether bond. Therapeutic uses and methods are also provided in which the antibody-drug conjugate and a PARP1-selective inhibitor are administered in combination to a subject.

This invention provides an application of a tartary buckwheat antioxidant peptide as a PARP1 inhibitor. This tartary buckwheat antioxidant peptide (SEQ ID NO:1) is used to prepare a poly(ADP-ribose) polymerase 1 inhibitor, and is used to prepare a drug for preventing and / or improving diabetic retinopathy. The tartary buckwheat antioxidant peptide of this invention exerts multiple biological functions by inhibiting PARP1 / PAR: on the one hand, it reduces NAD... + On the one hand, it depletes nutrients, and on the other hand, it protects vascular endothelial function by inhibiting angiogenesis. This buckwheat antioxidant peptide can be used as a drug to prevent and / or improve diabetic retinopathy.

PARP1 inhibitor compounds have structure (I). y is 0, 1, or 2. Each X D Selected from C, N, O, or S. X ET and X EB Selected from C and N. Each R 1 and each R 4 Independently, it is absent, H, or an organic group. R 4 The groups do not fuse to form a ring. R 3 It is an H or organic group. L is (II). The ring C is aromatic. X A1 and X B3 Selected from C and N. Each X A2 X B2 and X C Selected from C, N, O, and S. The C ring is a heterocyclic ring. Each R... 5A R 5B and R 5C It is absent, H, or an organic group. R 6 It is an H or organic group. n, m, p, q, r, and s are integers, where n+m is 1 to 5, p+q is 2 to 6, and r+s is 3 or 4. Q 1 and Q 2 Each is an independent bond or linking group. (I)(II)

The present disclosure relates to compounds of Formula (I) and to prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods of preparation thereof. The compounds disclosed herein can be used to modulate PARP1 activity and can be used to treat conditions in which PARP1 activity is involved, such as cancer.

The present invention provides a PARP1 inhibitor represented by formula (I), or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, crystalline polymorph, hydrate, or solvate thereof. The present invention also provides a method for producing the compound, a pharmaceutical composition containing the compound, and the effect of the compound in the prevention and treatment of cancer, ischemic disease, or neurodegenerative disease. [C1] TIFF2026501329000048.tif53156

The invention discloses a TOP1-PARP1 double-target inhibitor as well as a preparation method and application of the TOP1-PARP1 double-target inhibitor. The TOP1-PARP1 double-target inhibitor is a compound as shown in a formula D or a stereoisomer, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or a co-crystal of the compound, the compound not only shows good TOP1 and PARP1 enzyme inhibitory activity, but also has certain anti-proliferative activity on solid tumors and hematoma in vitro, and especially shows excellent anti-tumor activity on bladder cancer; as a double-target antitumor drug based on TOP1 and PARP1, the compound has further research value. .

The application discloses application of MSC-sEVs in treatment of reduced ovarian reserve. By targeting and activating DNA repair genes (such as PARP1) and combining NAD+ metabolism regulation, the ovarian function and reproductive potential of DOR are significantly improved. The method has high safety and unique advantages, and provides an innovative treatment scheme for patients with ovarian reserve dysfunction.

Disclosed herein are novel compounds, geometric isomers thereof, or pharmaceutically acceptable salts thereof, which are capable of inhibiting poly(ADP-ribose) polymerases. Also disclosed are methods of treating diseases or conditions associated with dysregulation or abnormal activity of PARP.

Disclosed herein are compounds, compositions, and methods for treating cancer, inhibiting PARP1 and / or ATR, and / or the repair of DNA.

Disclosed are a pyridine amide compound as represented by formula I as a PARP1 inhibitor, an intermediate and a preparation method therefor. The preparation method for the compound as represented by formula (I) solves the problems of difficult access to raw materials of the pyridine amide compound as the PARP1 inhibitor, high technical requirements for the method, etc.

PARP1 inhibitor compounds have the structure: Formula (I), each of Z1, Z2 and Z3 is selected from C and N. R1 and R2 together form a 5-membered or 6-membered ring or each independently is absent or is an organic group. And R3 does not exist or is an organic group. R4 is an organic group. L has the following structure: formula (II). Each X2 is selected from C, N, O and S. N is 1 or 2; m is (3-n); p is 1, 2 or 3; q is (4-p); r is 1, 2 or 3; and s is (4-r). Ring A and B are non-aromatic. Ring C is aromatic. Each R5A group is independently absent; members of a pair of R5A groups that together form a bridging group; or an organic group. Each R5B and R5C is independently absent or is an organic group. The compounds are useful in medicine, for example in the treatment of cancer. (I) and (II).

The invention discloses an aryl alkyne compound and application thereof. The invention provides a compound as shown in a formula I or pharmaceutically acceptable salt thereof. The compound provided by the invention has a good inhibition effect on PARP1 enzyme.

The present application provides a class of PARP1 inhibitors represented by formula (I), or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof. The present application also provides a preparation method of the compound, a pharmaceutical composition comprising the compound, and the role of the compound in the prevention and treatment of cancer, ischemic disease or neurodegenerative disease.

The invention belongs to the technical field of biological medicines, and particularly relates to application of 1, 2, 3, 6-tetra-O-galloyl-B-D-glucose and derivatives thereof as antitumor drugs and / or tumor sensitizing drugs. The invention reveals for the first time that AARS1 can catalyze NMNAT1 to be subjected to lactic acid modification as a lactic acid modification enzyme, so that the interaction between AARS1 and PARP1 is enhanced, the PARP1 activity is promoted, and the drug resistance of tumor cells with homologous recombination repair defects to a PARP inhibitor is caused. Based on the new mechanism, the invention screens and verifies that the small molecule compound 1, 2, 3, 6-tetra-O-galloyl-beta-D-glucose can effectively inhibit the catalytic activity of AARS1 and reduce the lactic acid modification level of NMNAT1, thereby restoring the sensitivity of drug-resistant tumors to PARP inhibitors.