400 results about "PARP inhibitor" patented technology

The invention provides application of a PARPi sensitizer in treatment of malignant tumors, and particularly relates to the technical field of biological medicines. A large number of experiments prove that TRMT10A is crucial for recruitment from BRCA1 to DNA damage sites for the first time, so that HR repair is promoted. The deletion of TRMT10A inhibits HR repair, so that tumor cells are more sensitive to PARPi. The invention discloses that the expression of TRMT10A in mCRPC is up-regulated, and the TRMT10A is regulated and controlled by ubiquitin specific peptidase 10 (USP10). Spautin-1 significantly results in the deficiency of TRMT10A, and sensitizes the tumor to PARPi in both patient-derived xenograft (PDX) and cell-derived xenograft (CDX). The research reveals that the ATM-TRMT10A-BRCA1 axis plays an important role in sensibilization of the PARP inhibitor, and a new angle is provided for exploring synthesis lethality. The mechanism can be therapeutically utilized through the combination of PARPi and Spautin-1, which may benefit more extensive patients with non-BRCA malignant tumors, and has important clinical significance.

A compound as represented by formula I-1, a stereoisomer or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing same, and the use thereof as a PARP-1 inhibitor in the preparation of a drug for treating related diseases. Each group in formula I-1 is as defined in the description.

The disclosure relates to methods, compositions, and combinations for the treatment of endometrial cancer. Specifically, the disclosure relates to methods of treating endometrial cancer in a subject in need thereof, comprising administering to the subject one or more chemotherapy agents, an anti-PD-L1 antibody or an antigen-binding fragment thereof, and optionally a PARP inhibitor. The disclosure also relates to combinations for use in the treatment of endometrial cancer comprising one or more chemotherapy agents, an anti-PD-L1 antibody or an antigen-binding fragment thereof, and optionally a PARP inhibitor.

The invention provides a lipidosome, a preparation method thereof and application of the lipidosome in preparation of a medicine for treating PARP inhibitor-resistant breast cancer, and relates to the technical field of biology. The preparation method of the liposome provided by the invention comprises the following steps: under a stirring condition, injecting an ethanol solution dissolved with soybean phospholipid and cholesterol into a histidine aqueous solution for hydration, volatilizing an ethanol component after the hydration is finished, and carrying out ultrasonic treatment to prepare the liposome. The preparation method is simple and convenient, and the prepared liposome loaded with histidine is high in encapsulation efficiency. The research of the inventor finds that histidine metabolism reprogramming occurs in the PARPi resistance process of breast cancer cells, so that DNA synthesis repair is maintained. And after the PARPi-resistant breast cancer cells are treated by adopting the liposome disclosed by the invention, the histidine content in the breast cancer cells can be increased, so that the PARPi-resistant cells are sensitive to PARPi, and further the treatment on the PARPi-resistant breast cancer is realized.

This present disclosure is directed to poly (ADP-ribose) polymerase (PARP) inhibitor nanoparticle composition and methods of use and preparation thereof. PARP inhibitor dose reduction through combination treatment may be achieved using photodynamic therapy or photoimmunotherapy.

The present disclosure generally relates to new PARP inhibitors and their use in the treatment and prevention of cancer, and to compositions containing said derivatives and processes for their preparation.

The present invention relates to the field of tumor treatment and immunology biology. Provided are a pharmaceutical combination containing an anti-PD-1-anti-VEGFA bispecific antibody, and the use thereof. Specifically, the pharmaceutical combination comprises at least one bispecific antibody and at least one PARP inhibitor, wherein the bispecific antibody comprises a first protein functional region for targeting PD-1 and a second protein functional region for targeting VEGFA; and according to the EU numbering system, the heavy chain constant region of an immunoglobulin contained in the bispecific antibody is mutated at two sites, i.e. site 234 and site 235, and after mutation, the affinity constant of the bispecific antibody to FcγRI, FcγRIIa, FcγRIIIa and / or C1q is reduced compared with the affinity constant of the bispecific antibody thereto before mutation. The combined administration of the PARPi and the bispecific antibody has a significantly better therapeutic effect on tumors than the individual use of the PARPi or the bispecific antibody; and the present invention has good application prospects.

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 methods and compositions for treating cancer with a macrocyclic indazole compound in combination with at least one other cancer therapeutic, such as a Bcl-2 inhibitor, a FLT3 inhibitor, a KRAS inhibitor, an ALK inhibitor, a PARP inhibitor, an EGFR inhibitor, a chemotherapy, and the like.

The invention provides a multi-modal data integration and machine learning model for predicting the curative effect and prognosis of an ovarian cancer patient on a PARP inhibitor. The model comprises a data collection and processing module, a feature screening module, a model construction and prediction module and a model interpretation and application module. Data collection relates to clinical, pathological, biochemical indexes and the like, and feature screening is performed through correlation analysis, Cox regression and other methods. The model construction adopts random forest, logistic regression and other algorithms, and meta-learning is carried out through XGBoost or LightGBM. The performance of the model is evaluated through indexes such as AUC and accuracy, and the model is explained by using an SHAP value. According to the invention, the curative effect and prognosis of the PARP inhibitor by the ovarian cancer patient can be accurately predicted, and a scientific basis is provided for clinical treatment.

The invention discloses application of a compound containing a PAPR1 degradation agent and a BET inhibitor in preparation of antitumor drugs, and particularly relates to the technical field of biological medicines. The PAPR1 degradation agent is a compound which has tumor selectivity and induces PARP1 degradation based on a CRBN ligand, and pharmaceutically acceptable salts and hydrates thereof. The anti-tumor medicine composition comprises a novel PAPR1 degradation agent and a BET (Brunauer, Emmett and Teller) inhibitor. According to the compound disclosed by the invention, the BET inhibitor JQ1 is used for inhibiting the function of BET protein so as to inhibit DNA repair and influence the DNA damage level, and a strategy for selectively damaging homologous recombination repair of cancer cells is constructed, so that related tumors of non-BRCA gene mutation are sensitive to PARP inhibition, and the clinical application range of PARP targets is effectively expanded; in view of the fact that acquired homologous recombination repair and protein mutation are two most common resistance mechanisms for PARP inhibition, the PARP1 protein is effectively degraded by utilizing PARP1-PROTAC, and the resistance to PARP inhibitor treatment can be overcome.

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 relates to a quinoxalinone derivative targeting poly ADP ribose polymerase and an androgen receptor as well as a preparation method and application of the quinoxalinone derivative. The structural formula of the quinoxalinone derivative is as follows: # imgabs0 #, R1 is one of hydrogen, methoxyl, methyl and halogen, the substituent position of R1 is at least one of 5, 6, 7 and 8 sites of a quinoxalinone ring, and X is a carbon atom or a nitrogen atom. The quinoxalinone derivative provided by the invention can be used as an active photosensitizer, a PARP inhibitor and an androgen receptor antagonist and can induce cell synthesis and death, and the process can improve the oxidation state and oxygen concentration in cells and improve the hypoxic microenvironment in tumors, so that the photodynamic therapy effect is further enhanced, namely, the effect of the quinoxalinone derivative is improved. The PDT therapy and the PARP inhibitor have a synergistic effect.

The present invention relates to a new pharmaceutical composition for the treatment and prophylaxis of a glioma comprising a first active agent combined with at least a second active agent, wherein the combination of said first and said second active agent results in a synergistic effect. The present invention also relates to a first active agent combined with at least a second active agent for use in the treatment and prophylaxis of a glioma wherein the combination of said first and said second active agent results in a synergistic effect. Finally, the invention relates to a method of treatment and prophylaxis of glioma in a subject in need, comprising the administration to the subject of said pharmaceutical composition or the combination of said first and said second active agent. The first agent is ATR inhibitor and the second agent is chosen from: cytostatic agent, GSK-3 inhibitor, mTOR inhibitor and PARP inhibitor.

Provided in the present invention are a pyridinopyrazole derivative pharmaceutical composition as shown in formula (I), and the use thereof in the preparation of an anti-tumor drug. The pharmaceutical composition comprises a compound of formula (I) and a PARP inhibitor.

The present invention provides a method for treating a cancer by using TH-302 and an analogue thereof alone or in combination with a PARP inhibitor, wherein in particular, TH-302 is used alone for treating a cancer patient sensitive to the PARP inhibitor, and TH-302 is used in combination with the PARP inhibitor for treating a cancer patient.

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 present invention relates to the use of small molecule compounds that allosterically inhibit ALC1 (CHD1L), in particular two classes allosteric inhibitors of ALC1 (CHD1L), of Formula (I) and Formula (II), that show a potentiating, preferably additive effect in the treatment of proliferative disease when combined with several classes of cancer drugs, namely inhibitors of Topoisomerase I, Topoisomerase II, ATM, ATR, Wee1, BRD, and MEK, or when combined with mitomycin C, paclitaxel, with ionizing radiation, or with an antibody drug conjugate with a tumor specific antibody conjugated to a TOP1 inhibitor. Furthermore, the present invention relates to said inhibitors of ALC1 of Formula (II) that show a synergistic effect in the treatment of pancreatic cancer or fallopian tube cancer when combined with a PARP inhibitor (Poly(ADP-ribose)-Polymerase inhibitor (PARPi)). By being synergistic with the function of said cancer drugs, said ALC1 inhibitors, in particular those of Formula (I) and Formula (II), potentiate the cancer cell killing properties of the aforementioned cancer drugs, in particular enabling therapeutic approaches where any of the aforementioned inhibitors is already used as part of the standard of care.

The invention belongs to the technical field of protein polypeptides, and particularly relates to a polypeptide targeting BRCA2 protein, application of the polypeptide and a medicine for treating prostatic cancer. The amino acid sequence of the polypeptide is shown as SEQ ID NO.1, the polypeptide has high binding capacity with BRCA2 protein, cell proliferation and tumor growth can be effectively inhibited when the polypeptide is delivered to prostatic cancer, and meanwhile the polypeptide has the capacity of degrading BRCA2 in a targeted mode. The combined application of the polypeptide and the PARP inhibitor can enhance the sensitivity of prostate cancer cells to the PARP inhibitor. Therefore, the polypeptide can be applied to preparation of a medicine for treating metastatic castration-resistant prostate cancer or preparation of a reagent for degrading the BRCA2 protein. The BRCA2 targeting PROTAC medicine can provide a new treatment strategy for prostatic cancer treatment, and the PARP targeting inhibitor is combined to provide a PARP inhibitor synthesis lethal treatment effect for metastatic castration resistant prostatic cancer patients.

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.