138 results about "PARP inhibitor" patented technology

The invention discloses a drug-combined anticancer composition and application of the composition in preparation of anticancer drugs. According to the present invention, the drug combination composition comprises the PARP inhibitor Olaparib and the calcium ion antagonist amlodipine maleate, the PARP inhibitor Olaparib and the calcium ion antagonist amlodipine maleate provide the synergistic effect, and compared with the single PARP inhibitor, the drug combination composition has characteristics of high stomach cancer sensitivity, significant gastric cancer efficiency improving, and wide application prospect. The Amlodipine in the drug combination composition provided by the invention enhances the curative effect of the PARP inhibitor Olaparib on the gastric cancer.

The present provides a method of treating ovarian cancer, breast cancer, gastrointestinal cancer, lung cancer, cancer of the brain or prostate cancer in a subject in need thereof, comprising administering to the subject a first amount of a selective PARP1 inhibitor or a pharmaceutically acceptable salt thereof, and a second amount of an ATR inhibitor or a pharmaceutically acceptable salt thereof. Also disclosed are compositions and kits comprising a PARP inhibitor and ATR inhibitor.

The invention discloses an application of a composition of a polypeptide and a PARP inhibitor in preparation of a medicine for treating breast cancer, the sequence of the polypeptide is as shown in SEQ ID NO: 1, and the PARP inhibitor is Olaparil or taprazopalil. The polypeptide can down-regulate the expression of the DNA damage repair gene FANCD2 protein and block the cross-linking damage repair between DNA chains. The PARP inhibitor blocks DNA single-stranded fracture damage repair by inhibiting the catalytic activity of PARP, and is mainly used for breast cancer treatment of BRCA mutation. DNA damage caused by the polypeptide and the PARP inhibitor in two different modes jointly destroys a cell replication fork protection mechanism, so that a DNA replication fork of a breast cancer cell is prone to stagnation and collapse, and cell death is caused. The invention shows synergistic cancer suppression activity in both BRCA wild type and BRCA mutant breast cancer subtypes, and is expected to provide a new treatment strategy for clinical treatment of breast cancer.

This disclosure features structurally-stabilized and / or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and / or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and / or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1 / 2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2 / BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

The disclosure provides substituted nitrogen containing tricyclic compounds as PARP inhibitors and the use thereof. This disclosure provides compounds represented by Formula (I) as below, wherein, the ring Z, Z1, Z2, Z3, Z4, Z5, A1, A2, A3, L, m, n, ring B and Cy are defined herein. The compounds of Formula I of the present disclosure are PARP inhibitors and thus are useful in the treatment of diseases, disorders and conditions, such as cancer, responsive to the inhibition of PARP activity. The present disclosure also relates to a pharmaceutical composition comprising the compound of Formula I and the use of the compound of Formula I in the preparation of a medicament for the treatment or prevention of diseases or conditions responsive to the inhibition of PARP activity.

The present disclosure relates to biodegradable polymeric microspheres comprising a biodegradable polymer and an immunotherapeutic agent selected from the group consisting of a poly ADP ribose polymerase inhibitor (PARP inhibitor) and / or a Toll-like receptor (TLR) agonist, wherein (a) 50% of the total amount of the immunotherapeutic agent in the biodegradable polymer microspheres is released from the biodegradable polymer microspheres to a PBS solution containing 0.05% of Tween 20 at 37 DEG C at a certain time point between 3 days and 14 days; (b) releasing the immunotherapeutic agent with the dry weight of 1 mg / g to 100 mg / g from the biodegradable polymer microspheres to a PBS solution containing 0.05% of Tween 20 at 37 DEG C at a certain time point between 3 days and 14 days; or (c) satisfies both (a) and (b). Other aspects of the present disclosure relate to methods of using such microparticles and kits comprising such microparticles.

The invention discloses a PARP inhibitor containing a beta-carboline structure, a synthesis method of the PARP inhibitor and application of the PARP inhibitor in preparation of a medicine for resisting triple negative breast cancer. The structural formula of the PARP inhibitor containing the beta-carboline structure is shown in the specification. The invention further specifically discloses the synthesis method of the PARP inhibitor containing the beta-carboline structure and application of the PARP inhibitor containing the beta-carboline structure in preparation of the medicine for resisting triple negative breast cancer. The synthesized PARP inhibitor containing the beta-carboline structure has relatively high inhibitory activity on the triple negative breast cancer and PARP, and a new way is provided for treatment of the triple negative breast cancer. The synthesis method of the PARP inhibitor containing the carboline structure is simple, raw materials are cheap and easy to obtain, and industrial production and clinical conversion are easy.

The present disclosure relates to compounds according to Formula I or a pharmaceutically acceptable salt and / or solvate thereof, wherein X 1 is H, F, or CI; R 1 is H, alkyl, or cycloalkyl; R 2 is H, alkyl, or cycloalkyl; R 3 is H, halo, alkyl, cycloalkyl, heterocyclyl, heteroaryl, or N(R 4 )(R 5 ); and one of R 4 and R 5 is H, alkyl, cycloalkyl, heterocyclyl, or heteroaryl, and the remaining one of R 1 and R 2 is H or alkyl, or R 4 and R 5 together with the nitrogen atom to which they are bound are heterocyclyl or heteroaryl. Furthermore, the present disclosure demonstrates that the compounds of the present disclosure penetrate the central nervous system, thereby allowing for the treatment of central nervous system cancers.

This invention belongs to the field of antitumor drug technology, specifically relating to PARP inhibitor-quinoline carboxylic acid coupled derivative compounds, their preparation methods, and uses. This invention synthesizes a novel polyADP-ribose polymerase (PARP) inhibitor derivative, the structure of which includes: a first structural unit with the clinical PARP inhibitor olaparib as the core backbone, a linker arm L, and a quinoline carboxylic acid fragment R; wherein the structural types and substituents of the linker arm L and the quinoline carboxylic acid fragment R are adjustable. This invention also provides a method for preparing the compound, which is characterized by simple steps, strong versatility, and ease of structural expansion, suitable for constructing compound libraries with different combinations of linker arms and different quinoline carboxylic acid fragments. The compound can be used to prepare drugs or drug compositions for inhibiting tumor cell proliferation and treating tumor-related diseases, showing excellent application prospects.

The present invention relates to a pharmaceutical combination comprising a PARP inhibitor and a compound of formula (I), or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof, for use in a method of treating HR-functioning cancer, the pharmaceutical combination comprising a PARP inhibitor and a compound of formula (I): or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof;

The invention relates to application of a PARP inhibitor in cancer treatment, in particular to application of the PARP inhibitor in ovarian cancer maintenance treatment. More specifically, the present invention provides a maintenance therapy for an ovarian cancer patient comprising administering an effective amount of 5-fluoro-1-(4-fluoro-3-(4-(pyrimidin-2-yl) piperazine-1-carbonyl) benzyl) quinazoline-2, 4 (1H, 3H)-dione, a hydrate or a pharmaceutically acceptable salt thereof, to an ovarian cancer patient who has undergone a first-line platinum-containing regimen treatment and achieves complete or partial remission, or a pharmaceutical composition containing 5-fluoro-1-(4-fluoro-3-(4-(pyrimidin-2-yl) piperazine-1-carbonyl) benzyl) quinazoline-2, 4 (1H, 3H)-dione, a hydrate thereof, or a pharmaceutically acceptable salt thereof, or a medicament containing the pharmaceutical composition.

Provided are methods and compositions, for treating prostate cancer by administering to a patient in need thereof a therapeutically effective amount of a PARP inhibitor, e.g., niraparib; a therapeutically effective amount of a CYP17 inhibitor, e.g., abiraterone acetate, and a therapeutically effective amount of a glucocorticoid, e.g., prednisone.

This disclosure relates to pharmaceutical combinations for treating and / or preventing cancer and methods and uses thereof. More particularly, provided are pharmaceutical combination comprising a PRMT5 Inhibitor and a cellular activity modulator selected from an EGFR inhibitor, a KRAS inhibitor, a KRAS-G12C inhibitor, a MEK inhibitor, a Bcl-2 inhibitor, a SOS1 inhibitor, a PARP inhibitor, a RAF inhibitor, a ERK inhibitor, a CDK4 / 6 inhibitor, a MALT1 inhibitor, a BTK inhibitor, MAT2A inhibitor, a PI3K inhibitor, a AKT inhibitor, a FGFR inhibitor, a Type I PRMT inhibitor, a STING agonist, or an immune checkpoint inhibitor / modulator.

The invention relates to an application of aloe-emodin. The invention provides an application of aloe-emodin in preparation of a PARP (poly-ADP-ribose polymerase) inhibitor. The aloe-emodin provided by the invention has relatively good inhibitory activity on PARP (Poly ADP-ribose Polymerase Chain Reaction).

Described herein are methods for treating cancer in a patient, the methods comprising administering to the patient a PRMT5 inhibitor and a PARP inhibitor, a KRAS inhibitor, or a kinase-like protein 18A (KIF18A) inhibitor, or a kinase inhibitor.

To provide a therapeutic agent for PARP inhibitor-resistant cancer.SOLUTION: The present invention relates to a pharmaceutical composition for treating or preventing a solid cancer patient having resistance to a PARP inhibitor, and the pharmaceutical composition according to the present invention can effectively reduce the size of a tumor in a patient having resistance to a PARP inhibitor.SELECTED DRAWING: Figure 4

The present invention relates to the technical field of chemical medicine, and disclosed are a crystal form of a heterocyclic deuterated compound as a PARP inhibitor, and a preparation method therefor and a use thereof. The present invention provides multiple crystal forms of a compound of formula (1), and a preparation method therefor and a use thereof. The present invention provides support for dosage form research by studying crystal forms I, II, III, and IV of the compound, thereby effectively preventing / treating PARP-related diseases and meeting different clinical medication needs.

The present invention relates to a PARP inhibitor, a combination of Omomyc, a functionally equivalent variant thereof, a conjugate comprising Omomyc or the functionally equivalent variant, a polynucleotide encoding the polypeptide, a vector comprising the polynucleotide, and a combination of cells capable of secreting the polypeptide or conjugate. The present invention also relates to pharmaceutical compositions containing the combinations of the present invention, and their medical use, specifically their use in the treatment of cancer.

Provided in the present application are an antibody-drug conjugate, and a preparation method therefor and the use thereof. The antibody-drug conjugate has a structure as represented by the following formula (III) or formula (IV). The drug is selected from a DNA topoisomerase inhibitor, a DNA intercalator, an RNA polymerase inhibitor, and a PARP inhibitor. The prepared antibody-drug conjugate exhibits a relatively good drug-to-antibody ratio and good targeted killing effects on breast cancer, gastric cancer, and lung cancer (e.g., non-small cell lung cancer, specifically lung adenocarcinoma).

The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and / or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and / or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

A method for treating a homologous recombination (HR)-deficient cancer, a homologous recombination (HR)-proficient cancer or a cancer that is resistant to DNA repair and DNA damage response (DDR) inhibitor therapy, such as Poly (ADP-Ribose) Polymerase (PARP) inhibitor therapy, is provided, the method comprising administering to a subject an RNA-binding motif protein 39 (RBM39) degrader, such as an aryl sulfonamide. A DDR inhibitor, such as a PARP inhibitor, may also be administered. A composition comprising a RBM39 degrader, such as an aryl sulfonamide, e.g., E7820 or Compound A, and a DDR inhibitor, such as a PARP inhibitor, is also provided.

The present invention relates to compounds and compositions containing said compounds acting as PARP inhibitors (Poly (ADP-ribose) polymerase). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.

The invention belongs to the field of biological medicine, and particularly relates to a pharmaceutical composition composed of HID-1121 and a PARP inhibitor and application of the pharmaceutical composition. The invention provides a drug combination composition of HID-1121 and a PARP inhibitor, and a better treatment effect is achieved through the synergistic effect of the drugs.

Described herein are injectable or infusible formulations of PARP inhibitors. In one aspect, the formulation comprises a PARP inhibitor and a cyclodextrin. The injectable or infusible PARP inhibitor-cyclodextrin formulation improves drug solubility, bioavailability, and therapeutic effectiveness. Also described herein are methods for treating oncological and non-oncological indications with injectable or infusible formulations of PARP inhibitors.

The present invention relates to a crystal form of a compound N-cyclopropyl-5-(4-((7-ethyl-6-oxo-5.6-dihydro-1.5-naphthyridin-3-yl)methyl)piperazin-1-yl)pyridine carboxamide and a preparation method therefor, and the use thereof in the preparation of a related drug.

Provided is a drug for treating triple negative breast cancer. Provided is use of a diamine E3 ligase ligand-based protein degradation agent targeting an androgen receptor in the preparation of a drug for preventing and / or treating triple negative breast cancer (including androgen receptor positive triple negative breast cancer). Provided is use of a diamine E3 ligase ligand-based protein degradation agent of an androgen receptor in combination with a targeting drug (comprising a PI3Kα inhibitor and a PARP inhibitor), an immunotherapy drug or a chemotherapeutic drug in the preparation of a drug for preventing and / or treating triple negative breast cancer.

The application discloses an anticancer composition of combined medication, and application of the composition in preparation of an anticancer drug. The combined medication composition provided by the application comprises a PARP inhibitor, Olaparib, and a calcium ion antagonist, Amlodipine maleate, and the two components have a synergistic effect, have higher sensitivity to gastric cancer compared with a single PARP inhibitor, and significantly improve the effective rate, thereby having a wide application prospect. The Amlodipine in the combined medication composition provided by the application enhances the curative effect of the PARP inhibitor, Olaparib, on gastric cancer.

Biomarkers, systems, and methods for predicting a prognostic outcome of pancreatic duct adenocarcinoma (PDAC) and responsiveness of a cancer patient to a PARP inhibitor are provided. The metabolites biomarkers are used to predicting a prognostic outcome of PDAC, and includes one or more of LysoPC (14: 0), LysoPC (18: 2), LysoPC (18: 1), Androsterone sulfate, alpha-CEHC, Glycodeoxycholic acid sulfate, LysoPC (20: 5), LysoPE (22: 5), and LysoPE (16: 1). The gene biomarkers are used to identify cancer patients responsive to a PARP inhibitor, and includes one or more of CTNND1, THRAP3, BRAF, STAT5B, and EXT2.

Bioadhesive and biodegradable polymeric nanoparticles can be administered intrathecally, for example, via the cisterna magna, into the spinal column to allow widespread distribution for the treatment of tumors such as leptomeningeal metastases. The nanoparticles rapidly spread to all cerebrospinal fluid (CSF) compartments, including the brain parenchyma and spinal column. The bioadhesive nanoparticles penetrate and are retained for long periods of time, during which time they can continue to release drugs. These nanoparticles can be loaded with different therapeutic, preventive, or diagnostic agents, most preferably DNA repair inhibitors, to enhance the killing of leptomeningeal tumors, such as leptomeningeal metastases, and disseminated tumors, such as medulloblastoma. In a preferred embodiment, patients are treated with a combination of a PARP inhibitor and temozolomide.

The invention belongs to the technical field of biological medicine, and particularly relates to application of REXO4 interference polypeptide in tumor treatment. It is found for the first time that the REXO4 interference polypeptide can inhibit breast cancer tumor cell proliferation, promote chemotherapy drug-induced DNA damage and improve the breast cancer chemotherapy effect, in addition, through combination of the REXO4 interference polypeptide and Olaparib, the remarkable synergistic anti-tumor effect can be shown, and the effect is better than that of single medication. The invention also finds that the REXO4 interference polypeptide can reverse the drug resistance of breast cancer to chemotherapeutic drugs, and a brand new solution is provided for overcoming the drug resistance of PARP inhibitors.