30 results about "Bcl-2 Inhibitor" patented technology

A method for classifying cancer patients as eligible to receive cancer therapy with a small molecule inhibitor of Bcl-2 comprising determination of the presence or absence in a patient tissue sample of chromosomal copy number status at the chromosomal locus 13q14 comprising the microRNA's miR-15a and miR-16-1 or at the chromosomal locus 11q23.1 comprising the microRNA miR-34c. The classification of cancer patients based upon the presence or absence of 13q14 loss or gain allows better selection of patients to receive chemotherapy with a small molecule Bcl-2 inhibitor such as N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl) methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl) methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide, and for monitoring patient response to this therapy.

Provided herein are methods that relate to a therapeutic strategy for treatment of cancer, including hematological malignancies. In particular, the methods include administration entospletinib and a Bcl-2 inhibitor, such as venetoclax, navitoclax, and ABT-737.

The invention discloses a new synthesis method for a BCL-2 inhibitor Venetoclax. The synthesis method includes the steps that 2,4-difluoro methyl benzoate serves as a raw material, the 2,4-difluoro methyl benzoate and 5-hydroxy-7-azaindole are subjected to a condensation reaction, Ven-16 is obtained, and 4-substituted isomer and other impurities are removed through recrystallization; the product and N-Boc-piperazine are reacted and hydrolyzed, and Ven-18 is obtained; Ven-18 and Ven-21 are condensed, Boc of trifluoroacetic acid is removed, and Ven-20 is obtained; the product and Ven-7 are reacted, reaction intermediates in all the steps have the good crystal forms, purification can be carried out through crystal to achieve the center control requirements of the technology, and a final product Venetoclax can also be subjected to recrystallization to obtain the product Venetoclax, wherein the HPLC purity of the Venetoclax is larger than 99.5%, and the individual impurity of the Venetoclax is smaller than 0.1%; the Venetoclax has the industrialized application value.

The invention discloses a synthesis method of a Bcl-2 inhibitor ABT-199. The method comprises the following steps: by using methyl 2-fluoro-4-nitrobenzoate and 5-hydroxy-7-azaindole as raw materials, carrying out substitution, reduction, cyclization, substitution, hydrolysis, condensation and the like to synthesize the ABT-199. The method has the characteristics of mild reaction conditions, simple operating technique, low cost and high yield.

The invention relates to a pharmaceutical composition containing artemisinin, artemisinin derivatives and a Bcl-2 inhibitor and application of the pharmaceutical composition in preparing medicines used for treating colorectal carcinoma, liver cancer, lung cancer, kidney cancer, stomach cancer, brain tumor, sarcoma, pancreas cancer, ovarian cancer, breast cancer or prostate cancer. The pharmaceutical composition provided in the invention has a remarkable synergistic effect, improves curative effects of drugs and reduces administration dosage and possibility of occurrence of side effects.

The invention discloses an application of a piericidin compound Piericidin A in preparation of anti-renal cancer drugs. The Piericidin A having the structure represented by the formula (I) has inhibitory effect with different intensities on three human renal cancer cell strains, especially has the strongest inhibitory activity on human adrenal carcinoma cells ACHN, and has the half inhibition rate IC50 reaching 0.40 [mu]M. Cell apoptosis experiments show that the Piericidin A can obviously induce late apoptosis of the human adrenal carcinoma cells ACHN, and a fact of inhibiting an anti-apoptosis protein Bcl-2 is one of anti-renal cancer action mechanisms. Therefore, the lead compound Piericidin A can be used as a Bcl-2 inhibitor for development of the anti-renal cancer drugs. The invention provides the new lead compound for development of new microbial-source anticancer drugs.

The present invention relates to a method of treating cancer and pre-cancerous syndromes in a human and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering:(i) an EZH2 inhibitor selected from:N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-[(1S)-1-methylpropyl]-6-[6-(1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide, or a pharmaceutically acceptable salt thereof1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pryidinyl)methyl]-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide, or a pharmaceutically acceptable salt thereof andN-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide, or a pharmaceutically acceptable salt thereof and(ii) a Bcl-2 inhibitor, to a human in need thereof.

The invention relates to a method for fast discovering lead compounds targeting Bcl-2 protein, which comprises the following steps of: 1) determining a combined site of the Bcl-2 protein and processing a three-dimensional structure; 2) establishing a small molecular ligand library for virtual screening; 3) establishing a computer virtual screening system aiming at the Bcl-2 protein; and 4) primarily determining 10 compounds having higher affinity with active sites by screening the mall molecular ligand library in the step 2) by using the step 3). By the method, the compounds with potential activity can be discovered in a short time, so the efficiency is greatly improved, and a basis is provided for researching and developing a novel anti-cancer medicament, namely a Bcl-2 inhibitor.

The present invention relates to a combination treatment for hematological cancers. More specifically; a combination of a telomerase inhibitor and a Bcl-2 inhibitor are useful in treating hematological cancers, including AML. In certain embodiments, the telomerase inhibitor is imetelstat or imetelstat sodium and the Bcl-2 inhibitor is ABT-199.

The invention relates to a preparation method of an intermediate needed for preparing a Bcl-2 inhibitor venetoclax. The synthetic route is represented as follows, and specifically comprises the following steps: using a compound I 2,4-difluorobenzoic acid as a raw material, performing hydroxylation and methyl esterification reactions to obtain a compound II methyl 4-fluoro-2-hydroxybenzoate; performing coupling on the compound II and piperazine to obtain a compound III; performing a reaction on the compound III with a raw material IV to obtain a compound V; and performing C-O coupling on the compound V and a compound VI 5-bromo-7-azaindole to obtain a compound VII, which is the intermediate. The preparation method provided by the invention has a mild reaction condition, has simple operation, is environmental friendly and high efficient, has low cost and is easy for large-scale production.

The disclosure includes compounds of Formula (I)wherein W, R1, R2, R3, R4, R5, R6, m, n, L, and Z1, are defined herein. Also disclosed is a method for treating a neoplastic disease and autoimmune disease with these compounds.

The invention discloses a substituted indole-2-carboxylic acid Bcl-2 small-molecule fluorescent probe and application thereof. Structural general formulas of the fluorescent probe is shown as follows:a general formula I and a general formula II are shown in the description; in the general formula I, R1 is each fluorescent group; R2 is halogen; in the general formula II, R3 is each fluorescent group; R4 is halogen. The small-molecule fluorescent probe can be used as a probe for identifying Bcl-2 family protein and used for researching physiology, pathology and related diseases related to Bcl-2; the small-molecule fluorescent probe can be used for high-flux screening of a Bcl-2 inhibitor and anti-tumor aspects, and also can be used for marking the Bcl-2 family protein and tumor cells or tissues which are highly expressed by the Bcl-2 family protein. Furthermore, a preparation method of the compound has the advantages of moderate reaction conditions, cheap and easy-to-obtain raw materials and simplicity in operation and post-treatment.

This invention relates to treatment of cancer using antibody drug conjugates that comprise PBD molecules in combination with Bcl-2 inhibitors.

Methods for treatment of cancer, including hematological malignancies. In particular, the methods include administration of a BTK inhibitor and a BCL-2 inhibitor or pharmaceutically acceptable salts or hydrates thereof, a Btk inhibitor and a Syk inhibitor or pharmaceutically acceptable salts or hydrates thereof, and administration of a Btk inhibitor and a P13K inhibitor or pharmaceutically acceptable salts or hydrates thereof.

The disclosure includes compounds of Formula (I)wherein W, R1, R2, R3, R4, R5, R6, m, n, L, and Z1, are defined herein. Also disclosed is a method for treating a neoplastic disease and autoimmune disease with these compounds.

The invention discloses a 3,5-disubstituted rhodanine anti-apoptosis protein Bc1-2 inhibitor as well as preparation method and an application thereof. The compound has a structure of a general formula I. The compound disclosed by the invention has high inhibitory activity on Bc1-2 and can be used for preparation of medicines for preventing or treating related mammal diseases caused by abnormal expression of anti-apoptosis protein Bc1-2. The invention also relates to a pharmaceutical application of a composition of the compound with the structure of the general formula I. The structural formula is as shown in the specification.

A method for the treatment of cancer by administering a therapeutically effective amount of a cyclin-dependent kinase (CDK) inhibitor with a therapeutically effective amount of a B cell chronic lymphocytic leukemia / lymphoma 2 inhibitor (“B Cell CLL / Lymphoma 2”, or “BCL-2”). Administration of the CDK inhibitor and BCL-2 inhibitor can be simultaneous, successive or separate.

The present disclosure pertains to a pharmaceutical combination comprising (a) an alpha-isoform specific PI3K inhibitor, (b) an MDM2 inhibitor, and optionally (c) a BCL-2 inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer a subject in need thereof comprising administering a therapeutically effective amount of such combination.

This invention pertains to a method for the treatment of cancer in a subject comprising administering to the subject an effective amount of a selective BCL-2 inhibitor or a prodrug or pharmaceutically acceptable salt thereof in combination with an effective amount of an anti-PD-1 antibody or an anti-PD-L1 antibody.

The present invention is directed to a combination therapy involving an anti-HER2 antibody-drug conjugate and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a HER2-expressing cancer.

The invention relates to a preparation method of an intermediate needed for preparing a Bcl-2 inhibitor venetoclax. The synthetic route is represented as follows, and specifically comprises the following steps: using a compound I 2,4-difluorobenzoic acid as a raw material, performing hydroxylation and methyl esterification reactions to obtain a compound II methyl 4-fluoro-2-hydroxybenzoate; performing coupling on the compound II and piperazine to obtain a compound III; performing a reaction on the compound III with a raw material IV to obtain a compound V; and performing C-O coupling on the compound V and a compound VI 5-bromo-7-azaindole to obtain a compound VII, which is the intermediate. The preparation method provided by the invention has a mild reaction condition, has simple operation, is environmental friendly and high efficient, has low cost and is easy for large-scale production.

The invention relates to a medicine composition containing a hepatic cell growth factor receptor (cMet) inhibitor and a Bcl-2 inhibitor and an application of the medicine composition in preparing medicine for treating colon cancers, liver cancers, lung cancers, kidney cancers, stomach cancers, brain tumors, sarcoma, glioma, pancreatic cancers, ovarian cancers, breast cancers or prostate cancers. The medicine composition containing the cMet inhibitor and the Bcl-2 inhibitor has a remarkable synergistic effect, and thereby the curative effect of medicine is improved, the medicine dosage is reduced and the side effect is reduced.

This invention relates to compounds, compositions and methods for treating leukemia, such as acute myeloid leukemia, in subjects where one or more mutations in FLT3 kinase are present.