196 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 disclosure relates to anti-VEGF antibodies in combination with PARP inhibitors for the treatment of tumors. Specifically, the invention relates to application of a compound as shown in a formula 1 or a pharmaceutically acceptable salt thereof and an anti-VEGF antibody in preparation of medicines for treating tumors. # imgabs0 #

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 provides an application of combination of cryptotanshinone and a PARP inhibitor in preparation of a medicine for treating tumors. The invention also provides a pharmaceutical composition for treating breast cancer, which contains cryptotanshinone and olaparib in a molar ratio of (4-32): (4-32) or (0.5-4): (2-16). The combination of the natural active product cryptotanshinone with slight toxic and side effects and olaparib is used for treating the triple-negative breast cancer, so that the DNA damage degree of tumor cells can be enhanced, and the apoptosis level of the tumor cells can be increased. Besides, cryptotanshinone can promote degradation of PARP inhibitor drug-resistant key protein RAD51, has a certain effect on inhibiting and reversing Olaparib drug resistance, and has a good application prospect in treatment of malignant triple negative breast cancer through synergistic interaction of Olaparib.

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.

The invention discloses application of SNRPD3 in preparation of a medicine for treating ovarian cancer, and belongs to the technical field of biological medicine. The invention provides application of a reagent for inhibiting or down-regulating SNRPD3 expression in preparation of drugs for treatment or adjuvant treatment of ovarian cancer. The reagent is siRNA or an ASO drug targeting SNRPD3. The invention proves that the apoptosis of the serous ovarian cancer cells can be increased and the growth of transplanted tumors of the serous ovarian cancer cells in mice can be inhibited by interfering the expression of the SNRPD3; an ASO drug targeting SNRPD3 can reduce SNRPD3 expression, and in-vitro experiments prove that the ASO drug can inhibit malignant biological behaviors of ovarian cancer cells; the siRNA is combined to inhibit SNRPD3 and a PARP inhibitor (PARPi) to treat ovarian cancer cells, and in-vitro experiments prove that the apoptosis ratio of the ovarian cancer cells is obviously increased by combining the siRNA and the PARP inhibitor. The invention provides a new treatment approach for ovarian cancer treatment.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a tetravalent platinum compound as well as a preparation method and application thereof. The invention provides a tetravalent platinum compound. The tetravalent platinum compound has a structure shown as a formula a to a formula d, wherein linker is respectively connected with a Pt-containing mother nucleus and a PARP inhibitor through-O-C = O; the PARP inhibitor comprises a carboxyl-containing structure and a carboxyl-free structure; when the PARP inhibitor contains a carboxyl structure, the linker is when the PARP inhibitor does not contain the carboxyl structure, and the data of the linker as the embodiment shows that the tetravalent platinum compound provided by the invention has good anti-tumor activity and low tumor drug resistance when being used as the PARP inhibitor.

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.

Provided in the present invention are a compound of formula (I), a crystal form thereof, a preparation method therefor, a composition thereof, and the use of the crystal form and the composition in the preparation of related drugs.

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.

Provided are substituted 8-methylquinazolin-4(3H)-one compounds useful as PARP inhibitors for the treatment of cancer and asthma, as well as pharmaceutical compositions comprising them and methods for their synthesis.

The present disclosure relates to a method for selection of ovarian cancer patients for treatment with PARP inhibitors This involves 1) preparing whole slide images of tissues of ovarian cancer patient to be treated 2) training and validating AI model built on Resnet-50 to recognize morphological features from tiles of hematoxylin and eosin stained whole slide images of tissues featuring the presence of homologous recombination deficiency as annotated by next generation sequencing 3) using the model to extract morphological features from the tiles of hematoxylin and eosin stained whole slide images of tissues of ovarian cancer patients, generating tile level predictions, aggregating tile level predictions to generate a probability score and selecting the patient for treatment with PARP inhibitors 4) administering PARP inhibitors treatment to the patient selected based on probability score reaching a predetermined threshold. Computer systems to implement the method are also disclosed.

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;

Provided in the present invention are a compound of formula (I), a crystal form thereof, a preparation method therefor, a pharmaceutical composition thereof, and the use of the crystal form and the pharmaceutical composition in preparation of related drugs.

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.

Provided are substituted tricyclic compounds as PARP inhibitors and the use thereof. The compounds represented by Formula (I) as below, wherein, the ring Z, Z1, Z2, Z3, Z4, Z5, A1, A2, A3, L and Cy are defined herein. The compounds of Formula I 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 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 application relates to a method for increasing PARP inhibitor sensitivity, the method comprising a step for inhibiting the expression or activity of TRIM44.

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.