122 results about "PARP1" patented technology

The invention discloses a PARP1 / CDK6 double-target inhibitor as well as a preparation method and application thereof, the PARP1 / CDK6 double-target inhibitor is selected from a compound with a structure as shown in a formula I or pharmaceutically acceptable salt or solvate thereof, L is selected from # imgabs0 #, and R is selected from hydrogen, deuterium, halogen, hydroxyl, sulfydryl, cyano, nitro, methoxyl, C1-C8 alkyl or C3-C8 cycloalkyl. The PARP1 / CDK6 double-target inhibitor disclosed by the invention has a relatively good effect on human breast cancer cells, and keeps good in-vitro enzyme inhibition activity on CDK6 and PARP1. The invention discloses an application of a CDK6 / BRD4 double-target inhibitor in preparation of a medicine for treating PARP1 / CDK6 mediated diseases. The invention discloses an application of a PARP1 / CDK6 double-target inhibitor in preparation of a medicine for treating or preventing triple negative breast cancer. # imgabs1 #

Described herein are tricyclic PARP1 inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of cancer. Also disclosed herein is a method of treating brain cancer in a subject in need thereof, 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-penetrating.

A PARP1 inhibitor compound has a structure: (I) y is 0, 1, or 2. Each XD is selected from C, N, O or S. XET and XEB are selected from C and N. Each R1 and each R4 is independently absent, H, or an organic group. The R4 groups are not fused to form a ring. R3 is H or an organic group. L is: (II) Ring C is aromatic. XA1 and XB3 are selected from C and N. Each XA2, XB2 and XC is selected from C, N, O and S. Ring C is a heterocycle. Each R5A, R5B, and R5C is absent, H, or an organic group. R6 is H or an organic group. n, m, p, q, r and s are integers, with n+m being 1 to 5, p p+q being 2 to 6, and r+s being 3 or 4. Q1 and Q2 are each independently a bond or a linking group.

A PARP1 inhibitor compound has a structure of: Formul (i) A dotted line represents a single bond or a double bond, y is 0, 1, or 2. Each XD is selected from C, O, and N. No more than one XD is O. When an XD is O or N, ring D is non-aromatic. Each R1 is absent, H, or an organic group. Each R4 is absent; H; a halogen; C(R9)o-3; OR9; or S(R9)1-5. Each R9 is H or an organic group. R2 and R3 are each H or an organic group. L is: Formul (ii) Each X1, X3, X4 and X5 is C or N. Each X2 is C, N, O, or S. n+m and r+s are 2 to 5. p and q are each 1 to 3. p+q is 2 to 5. Each R5A, R5B, R5C, and R6 is absent, H, or an organic group. Q1 and Q2 are each independently a bond or linking group.

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.

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 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.

A PARP1-targeting compound represented by formula (I) and a use thereof, relating to the technical field of chemical medicines. The PARP1-targeting compound 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 brain penetration potential.

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 invention belongs to the field of medicines, and particularly relates to a PARP1 and ULK1 double-target inhibitor as well as a preparation method and application thereof. The compound as shown in the formula I or pharmaceutically acceptable salt, solvate, active metabolite, polymorphic substance, ester, optical isomer or prodrug of the compound, and a composition containing the compound as shown in the formula I show a very strong inhibition effect on PARP1 and ULK1; the compound prepared by the invention has a good inhibition effect on a plurality of tumors, such as triple negative breast cancer, liver cancer, ovarian cancer and the like, which are caused by Parp1 inhibitor induced autophagy and cause Parp1 inhibitor primary drug resistance.

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 discloses a heterocyclic-fused deuterated compound and application thereof, and belongs to the technical field of chemical medicines. The heterocycle deuterated compound as shown in the formula (I) provided by the invention can be used as a PARP1 inhibitor, has the advantages of high activity and high selectivity, and also has excellent pharmacokinetic properties and excellent safety. # imgabs0 #