32 results about "BET inhibitor" patented technology

The invention discloses the application of RVX-208 as an HIV-1 latent infection reversing agent, belongs to the field of medicine, and relates to the application of RVX-208 (Apabetalone, RVX-000222) as an HIV-1 latent infection reversing agent. An important reason why HIV‑1 is difficult to be completely eliminated in the body is that HIV‑1 can lurk in the resting memory CD4 + in T cells. The RVX-208 of the present invention has good activity of activating HIV-1 latent cell pool in vitro, especially can efficiently activate the latent virus pool in HIV-infected patients, and can activate latent infection reversal agents such as protein kinase C with other mechanisms of action Drugs, histone deacetylase inhibitors and cytokines have a good synergistic effect. Compared with the known BET inhibitor JQ1, its in vitro cytotoxicity is greatly reduced, and the drug is safe and well tolerated. Therefore, RVX‑208 is expected to become a new and efficient HIV‑1 latent infection activator, so as to achieve the goal of completely eradicating the HIV‑1 latent infection pool and realizing the "functional" cure of HIV.

The invention belongs to the medicine field and relates to the application of a bromine structural protein BET inhibitor to anti-HIV-1 latency treatment. Experiments prove that the chemical has an HIV-1 latent cell activation induction effect without causing activation of T cells of the whole body, can achieve synergetic activation after being combined with a protein kinase c agonist or cytokines, and can kill activated latent infected cells after being combined with antiretroviral drugs, so as to accelerate the elimination of a latent virus storage. Furthermore, the bromine structural domain protein inhibitor can be used for preparing anti-HIV-1 latency drugs and can provide a new interventional way and strategy for complete cure of AIDS.

The invention relates to a preparation method of new bifunctional small molecules and pharmaceutically acceptable salts, hydrates or prodrugs thereof, and application of the compounds and pharmaceutically compositions thereof in treatment of tumors, inflammation, immunity and other diseases. The bifunctional small molecules involved in the invention are protein degradation targeting chimeras (PROTACs), and can selectively induce BET (Bromo-and Extra-terminal) protein degradation. According to the invention, a carbon chain or polyethylene glycol chain truss arm is utilized to connect the 3, 5-dimethyl isoxazole BET protein small molecule inhibitor with the von Hippel-Lindau (VHL) protein ligand in an E3 ubiquitin ligase complex so as to obtain the bifunctional small molecules.

The invention relates to a preparation method of triazole derivatives and medical application of the triazole derivatives. The invention particularly relates to triazole derivatives disclosed as general formula (I) and pharmaceutical salts thereof or a pharmaceutical composition containing the triazole derivatives or pharmaceutical salts thereof, and a preparation method thereof, and further relates to application of the triazole derivatives and pharmaceutical salts thereof or pharmaceutical composition containing the triazole derivatives and pharmaceutical salts thereof as a BET inhibitor in treating multiple tumors.

The present invention relates to the use of NSD3i inhibitors for the treatment of cancer. In particular, the present invention relates to methods, kits and compositions comprising NSD3 inhibitors to treat cancers dependent on NSD3, in particular subjects with NUT midline carcinoma (NMC) and subjects with NSD3 / NUT or BRD4 / NUT or BRD3 / NUT fusion genes, as well as subjects with BRD4-dependent (but NUT-independent cancers). The present invention also relates to methods, kits and compositions comprising BET inhibitors for the treatment of subjects with NSD3 / NUT fusion genes. Other aspects of the invention relate to assays and methods to identify an inhibitor of NSD3 which disrupts or decreases the interaction of the NSD3 protein with the ET do main of BRD4.

The invention discloses a prostatic cancer marker SPOP. The SPOP marker comprises DNA of SPOP, mRNA or protein coded thereby, wherein the Pubmed Gene ID of the DNA sequence of the SPOP is 8405; the nucleotide sequence of the mRNA of the SPOP is shown as SEQ ID No.1; the protein sequence of the SPOP is shown as SEQ ID NO.2. The invention also discloses application of the SPOP marker in molecular subtyping of prostatic cancer and guiding of a BET inhibitor in treatment of prostatic cancer.

The invention discloses a pyrrole BET inhibitor and a preparation method and application thereof. The compound is a structure as shown in a general formula (I) or one or a mixture of more of a tautomer, a meso-mer, a raceme, an enantiomer and a diastereoisomer of the compound, or a pharmaceutically acceptable salt of the compound. According to the compound or the mixture thereof or the pharmaceutically acceptable salt thereof, ethyl acetoacetate derivatives and amino aryl ethyl ketone serve as starting raw materials, the compound of the general formula (I) is obtained through a continuous reaction, the preparation method is simple and convenient, the raw materials are easy to obtain, and the preparation method has good applicability, and the medicine taking the derivative as an active ingredient can be used in medicines for effectively preventing and / or treating BET protein related diseases.

Method for treating cardiac diseases using BET inhibitors including JQ1 are provided. Methods for treating cardiac hypertrophy, method for treating heart failure not arising from inflammation, methods for treating myocardial infarction, methods for cardioprotection and methods for inhibiting restenosis are described herein. The methods involve the use of effective amounts of BET inhibitors such as JQ1.

The present invention relates to covalent conjugates of BET inhibitors and alpha amino acid esters, processes for their preparation, compositions containing them, and to their use in the treatment of various disorders in particular inflammatory and autoimmune diseases, such as rheumatoid arthritis; and cancers.

The present disclosure provides combination therapy comprising a BET inhibitor and a protein phosphatase 2A (PP2A) activator, a B-cell lymphoma-2 (Bcl-2) inhibitor, a B-cell lymphoma-extra-large (Bcl-xl) inhibitor, a casein kinase 2 (CK2) inhibitor, and / or a mediator complex subunit 1 (MEDl) for cancer. The combination therapy is expected to be synergistic in treating the cancer, compared to the monotherapy. Methods for identifying a subject having a cancer that is resistant to or at risk of developing resistance to bromodomain and extra terminal (BET) inhibitor therapy are also provided.

The present disclosure provides BET inhibitors of the formula: wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods of treating a patient comprising administering a bromo- and extra-terminal (BET) domain inhibitor for the treatment of FSHD which modulates DUX4 expression. In some embodiments, the present methods comprise using one or more BET inhibitors as a therapeutic agent for the treatment of FSHD patients including patients who are being treated with one or more palliative treatments such as therapy and / or agents which lead to increased muscle mass.

This document provides methods and materials involved in identifying and treating mammals having a cancer resistant to BET inhibitors. For example, methods and materials for administering (a) one or more AKT inhibitors and / or one or more CDK inhibitors and / or one or more CBP / p300 inhibitors in combination with (b) one or more BET inhibitors to mammals identified as having a cancer resistant to treatment with one or more BET inhibitors in the absence of AKT, CDK, and CBP / p300 inhibitors are provided.

The invention discloses a preparation method and application of a protein degradation targeting chimera. The compound has a structure as shown in a general formula (I). The compound is reasonably designed through a BET inhibitor ((+)-JQ1), an HDAC inhibitor and E3 ubiquitin ligase. Pharmacological experiments show that the compounds have relatively strong binding inhibition activity on BET protein and HDAC protein and in-vitro anti-tumor proliferation activity. Mechanism experiments show that the compound BET / HDAC double-target PROTAC can obviously induce degradation of the BRD4 protein and the HDACs protein, and can be applied to tumor diseases with pathological characteristics mediated by the BRD4 protein and the HDACs protein. As a BET / HDAC double-target PROTAC molecule reported for the first time, the compound has further development and research values.

The invention relates to a method for promoting long-term stable passage of pancreas islet precursor cells and preparing pancreas islet cells and pancreas islet organs with mature functions in a large scale. According to the method, a culture medium at least containing a BET inhibitor and a TGF beta inhibitor is adopted to culture the pancreas islet precursor cells, so that the pancreas islet precursor cells can keep original characteristics after multiple passage, and the obtained pancreas islet cells and pancreas islet organs also have normal functions. Therefore, the islet precursor cells with stable and uniform quality can be massively prepared by the method disclosed by the invention, enough islet cells and islet organs can be further prepared, and the islet precursor cells can be used for disease modeling, drug screening and diabetes treatment and have a very wide application prospect.

The invention relates to application of a BET inhibitor BMS-986158, in particular to application of the BET inhibitor BMS-986158 in preparation of an anti-HIV-1 medicine. Researches show that the BET inhibitor BMS-986158 can be used for remarkably activating expression of HIV-1 in an HIV-1 latent cell line J-Lat, OM10.1 and ACH2 cells; when the the BET inhibitor BMS-986158 is combined with other types of latent activators, a synergistic effect is shown; the activation effect is not influenced by anti-HIV drugs, and activities of the anti-HIV drugs can be improved; and in peripheral blood mononuclear cells separated from a body of an HIV-1 patient receiving ART treatment for a long time, the BMS-986158 also shows a remarkable latent activation effect. Toxicity experiment of the BMS-986158 on PBMC shows that CC50 is greater than 100 [mu] M, indicating that the BMS-986158 less toxic to cells. The BMS-9861658 has low toxicity and high latent activation HIV-1 activity, and can enhance an antiviral effect of an anti-viral drug in vitro. Therefore, the BMS-9861658 can be used for preparing an anti-HIV-1 latency medicine and can be combined with an anti-HIV medicine to be used for treating the AIDS, and a new intervention way and strategy are provided for thoroughly curing AIDS.

The invention relates to the field of immunotherapy, more in particular to a composition for use in the treatment of cancer. The invention also relates to a composition obtainable by such a method, such as a pharmaceutical composition. More in particular, the invention relates to an ex vivo method for obtaining a composition suitable for the treatment of cancer in a subject, comprising the steps of providing primary tumor cells derived from the subject, and ex vivo contacting the tumor cells with an inhibitor of a bromodomain and extra-terminal domain family member (BET inhibitor).

The invention discloses a BET (bromodomain and extraterminal domain) / HDAC (histone deacetylase) double-target inhibitor, and a preparation method and application thereof. The structure of the double-target inhibitor is as shown in the specification, wherein n=2-6. Compared with the prior art, the double-target inhibitor has the advantage that pharmacophore of a BET inhibitor BI-2536 and pharmacophore of an HDAC inhibitor are spliced by a Linker to obtain a novel BET / HDAC inhibitor with BET / HDAC double-target inhibition effect. The preparation method is simple, mild in condition and easy to implement.

The present invention relates to the use of volasertib, or a pharmaceutically acceptable salt thereof or a hydrate thereof, in combination with a BET inhibitor, or a pharmaceutically acceptable salt thereof or a hydrate thereof for treating patients suffering from acute myeloid leukemia (AML).

Bromodomain and extra terminal protein (BET) resistant leukemic cell lines and methods for producing such cell lines are described as are methods for using such cell lines in screening assays to identify therapeutic agents. The cell lines can be generated from haematopoietic stem and progenitor cells (HSPCs) that are clonally enriched by serially exposing c-kit positive cells to a BET inhibitor.

The present invention is directed to the combination therapy of DLBCL with a BET inhibitor, a Bcl-2 inhibitor and an anti-CD20 antibody.

The invention discloses a tetravalent platinum complex containing a BET inhibitor. The structure of the tetravalent platinum complex is as shown in a general formula I, wherein substituent groups are defined in the specification. The advantages of the tetravalent platinum complex are utilized, and the synergistic anti-tumor effect of the BET inhibitor and cis-platinum is exerted. The tetravalent platinum complex containing the BET inhibitor shows broad-spectrum and excellent in-vitro anti-tumor activity, the activity of the tetravalent platinum complex is obviously superior to that of cis-platinum, the BET inhibitor and the mixture of the cis-platinum and the BET inhibitor according to the ratio of 1: 1, and the tetravalent platinum complex has huge potential of being developed into a novel broad-spectrum anti-tumor drug.

The invention discloses a preparation method and application of BETHDAC dual-targeting PROTAC. The compound has a structure as shown in a general formula (I). The compound is reasonably designed through a BET inhibitor ((+)-JQ1), an HDAC inhibitor and E3 ubiquitin ligase. Pharmacological experiments show that the compound has relatively strong binding inhibition activity on BET protein and HDAC protein and in-vitro anti-tumor proliferation activity. Mechanism experiments show that the compound BET / HDAC double-target PROTAC can obviously induce degradation of the BRD4 protein and the HDACs protein, and can be applied to tumor diseases with pathological characteristics mediated by the BRD4 protein and the HDACs protein. The compound as a BET / HDAC double-target PROTAC molecule reported for the first time has further development and research values.

The present invention relates to covalent conjugates of BET inhibitors and alpha amino acid esters, processes for their preparation, compositions containing them, and to their use in the treatment of various disorders in particular inflammatory and autoimmune diseases, such as rheumatoid arthritis; and cancers.

The invention discloses pyrrole BET inhibitors and a preparation method and application thereof. The compound is the structure shown in general formula (I) or one or more of its tautomers, mesomers, racemates, enantiomers and diastereomers mixture, or a pharmaceutically acceptable salt thereof. Such compounds or their mixtures or their pharmaceutically acceptable salts use ethyl acetoacetate derivatives and aminoaryl ethyl ketones as starting materials, and obtain the compound of general formula (I) through continuous reaction, and the preparation method thereof is relatively simple and convenient. The preparation method is easy to obtain and has good applicability, and the medicament with the derivative as the active ingredient can be effectively used in the medicament for preventing and / or treating diseases related to BET protein.

Provided herein are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-l- oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-l-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing multiple myeloma. The second active agent is one or more of a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an MEK inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BRD4 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an AURKB inhibitor, a BIRC5 inhibitor, a BET inhibitor, or a DNA methyltransferase inhibitor.

The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a BET (bromodomain and extra-terminal protein) inhibitor, or a pharmaceutically acceptable salt thereof, alone or in combination with one or more JAK inhibitors. Also provided are medicaments for use in treating cancer.

Provided herein are methods of using 4-(4-(4-((2-(2, 4-difluorophenyl)-1, 2 The present invention relates to a method of treating, preventing or managing multiple myeloma in combination with a first active agent, a second active agent, or an enantiomer, enantiomer mixture, tautomer, or pharmaceutically acceptable salt thereof. The present invention also relates to a method of treating, preventing or managing multiple myeloma in combination with a first active agent and an enantiomer, enantiomer mixture, tautomer, or pharmaceutically acceptable salt thereof, or an enantiomer, enantiomer mixture, tautomer, or pharmaceutically acceptable salt thereof. The second active agent is one or more of a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an MEK inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BRD4 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an AURKB inhibitor, a BIRC5 inhibitor, a BET inhibitor or a DNA methyltransferase inhibitor.