95 results about "PARP1" patented technology

The invention discloses a double-target PARP / CDK6 inhibitor and a preparation method and medical application thereof.The inhibitor comprises a compound with the structure shown in the general formula or pharmaceutically acceptable salt of the compound. The inhibitor can target PARP1 and CDK6 at the same time, can be used as a single therapeutic agent for tumors or can be combined with other anti-tumor drugs for use, and the application prospect is wide. Therefore, the effects of improving the curative effect of the existing anti-tumor drug and reducing the dosage and toxicity are achieved.

The invention provides a PARP1 inhibitor as shown in a formula (I), or pharmaceutically acceptable salts, isotope variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates of the PARP1 inhibitor. The invention also provides a preparation method of the compound, a pharmaceutical composition containing the compound, and an effect of the compound in prevention and treatment of cancers, ischemic diseases or neurodegenerative diseases. # imgabs0 #

The invention discloses a biaromatic ring amide compound and application thereof. The invention provides a compound as shown in a formula I or pharmaceutically acceptable salt thereof. The small molecule compound provided by the invention has a good inhibition effect on Pol theta enzyme and / or PARP1 enzyme, further has a relatively strong proliferation inhibition effect on DLD1BRCA2- / -cells, has an extremely weak proliferation inhibition effect on DLD1 wild-type cells and shows very good selectivity, and further, the compound provided by the invention can be used for overcoming drug resistance, reducing the dosage and reducing the toxic and side effects, and has a good application prospect. The purposes of expanding indications and improving the treatment effect are achieved. # imgabs0 #

The invention discloses an application of PARP1PROTACA19 in preparation of a medicine for preventing and treating acute kidney injury, and relates to the technical field of medicines, and the key points of the technical scheme are as follows: PARP1PROTAC A19 can reduce the expression level of PARP1 in HK2 cells and mice, reduce the levels of acute kidney injury markers KIM-1 and inflammatory factors of the HK2 cells and the mice, improve pathological changes of kidney tissues, and inhibit the occurrence of acute kidney injury. The traditional Chinese medicine composition has obvious prevention and treatment effects on acute kidney injury.

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.

The invention discloses a diabetic nephropathy marker PARP1, a primer combination and application, and relates to the technical field of biology. The sequence of the primer combination is PARP1-F, and is as shown in SEQ ID NO. 1; 1, PARP1-R as shown in SEQ ID NO. 2; an internal reference primer beta-actin-F, which is as shown in SEQ ID NO. 17; an internal reference primer beta-actin-R is as shown in SEQ ID NO. 18. The invention finds that the expression of PARP1 in the kidney tissue of a patient with diabetic nephropathy is increased and is positively correlated with ACR (Activated Receptor). The invention also finds that PARP1 is related to podocyte damage, and knocking down PARP1 can relieve podocyte endoplasmic reticulum stress and apoptosis, and can reflect the progress of DKD to a certain extent.

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.

Provided herein are certain fused polycyclic compounds having a polycyclic linker, such as compounds of Formula (I), as PARP1 inhibitors, pharmaceutical compositions comprising these compounds, and methods of using these compounds or pharmaceutical compositions in the treatment of diseases or conditions. # imgabs0 #

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.

The invention discloses a nitrogen-containing heterocyclic ring compound and medical application thereof. Specifically, the invention relates to a nitrogen-containing heterocyclic ring compound as shown in a general formula (I), a preparation method thereof, a pharmaceutical composition containing the nitrogen-containing heterocyclic ring compound and application of the nitrogen-containing heterocyclic ring compound serving as a poly ADP ribose polymerase 1 (PARP1) inhibitor to treatment of diseases related to PARP1 activity. Wherein the definition of each group in the general formula (I) is the same as that in the specification.

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

Disclosed herein is the compounds and pharmaceutically acceptable salts thereof that inhibit the Poly (ADP-ribose) polymerase (PARP) family of enzymes. The present disclosure also relates to the use of these compounds or pharmaceutically acceptable salts thereof in the treatment of diseases.

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.

To provide a method for treating a disease.SOLUTION: Tricyclic PARP1 inhibitors and pharmaceutical compositions comprising the inhibitors are described herein. The subject compounds and compositions are useful for the treatment of cancer. Also disclosed herein is a method for treating a subject in need of treatment of brain cancer, the method comprising administering a compound disclosed herein or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof. In some embodiments, the compound or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof is brain penetrant.SELECTED DRAWING: None

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.

The present disclosure provides crystal forms of PARP1 inhibitor 5-(4-((9-fluoro-4-oxo- 4,5-dihydropyrazolo[1,5-a]quinoxalin-7-yl)methyl)piperazin-l-yl)-N,6-dimethylpicolinamide and preparation method thereof. The crystal forms are applicable for the treatment or prevention of diseases or conditions such as cancer that respond to PARP1 activity inhibition.

Described herein are tricyclic PARP1 inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of cancer.

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

To provide PARP1 inhibitors and uses thereof.SOLUTION: Described herein are PARP1 inhibitors and pharmaceutical compositions comprising the inhibitors. Subject compounds and compositions are useful for the treatment of cancer. Also disclosed herein is a pharmaceutical composition comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and a pharmaceutically acceptable excipient. A method of treating a cancer that is present in the brain in a subject in need thereof comprises administering a compound disclosed herein, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.SELECTED DRAWING: None

The present invention discloses a DNA nanoprobe for imaging and treating triple-negative breast cancer, as well as its preparation method and application. The invention relates to the technical field of DNA nanoprobes. The DNA nanoprobe comprises a DNA double helix structure and doxorubicin loaded by embedding the DNA double helix structure. The DNA double helix structure is self-assembled by a T strand, a hairpin strand 1, and a hairpin strand 2 through a hybridization chain reaction. The T strand is an AS1411-functionalized T strand. The sequence of the hairpin strand 1 contains a PARP1 antisense sequence and is modified with a Cy5 fluorescent group. The hairpin strand 2 is modified with a PD-L1 siRNA and a BHQ2 fluorescence quencher. The present invention is expected to achieve integrated diagnosis and treatment of triple-negative breast cancer through AS1411 aptamer targeting, PARP1-triggered "off-on" fluorescence imaging, and a chemotherapy-gene-immunotherapy combined therapy strategy.