25 results about "BRD4" patented technology

The invention relates to a marker for predicting the prognosis of ovarian cancer and application thereof, and the marker is used for predicting the prognosis condition of ovarian cancer by detecting any one or more of BRD4, H4K12la and Ube2v1. Compared with the prior art, it is found for the first time that BRD4 can be used as a histone milk acylation transferase to enzymatically modify a histone lysine site H4K12, so that the histone lysine site H4K12 is subjected to milk acylation modification, then gene transcription of Ube2v1 is increased, and proliferation and growth of ovarian cancer cells are promoted. The invention not only discovers that BRD4 can be used as histone milk acylation transferase to play a new function of milk acylation modification, but also clarifies the effect of the BRD4-H4K12la-Ube2v1 pathway in the growth process of the ovarian cancer, and provides a new method for targeted therapy of the ovarian cancer.

The application discloses an EZH2 and BRD4 double-target inhibitor and application thereof, wherein the double-target inhibitor is obtained by coupling a structural fragment for inhibiting a BRD4 protein and a structural fragment for inhibiting an EZH2 protein through a linker. The inventors find that the structural fragment for inhibiting the EZH2 protein and the structural fragment for inhibiting the BRD4 protein are restructured, coupled together through the linker, and the length of the linker is adjusted, so that the obtained EZH2 and BRD4 double-target inhibitor has an unexpected anti-tumor effect, the anti-tumor effect is better than that of an individual EZH2 inhibitor or BRD4 inhibitor, and is also better than that of a combination of the two under the same conditions.

The application discloses a new use of a BET inhibitor YD-851 or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating pulmonary fibrosis. The application finds that YD-851 can inhibit the expression of BRD4 and fibrosis-related markers in pulmonary fibrosis tissues, reduce the structural damage of bleomycin-induced mouse lung tissues, inflammatory cell infiltration and fibrosis pathological changes, and improve lung function damage. Experimental results show that YD-851 can reduce the pulmonary fibrosis score, inflammation score and area ratio of consolidation, improve the lung imaging abnormalities, and down-regulate the expression of fibrosis-related genes such as Col1a1, Fn1 and Acta2. It is shown that YD-851 has the effect of treating pulmonary fibrosis, and can be used for preparing a drug for treating pulmonary fibrosis, and a new use of YD-851 is developed.

Provided herein are compositions and methods for treating an autoimmune disease or disorder in a subject. In some cases, the compositions and methods use chemical inducers of proximity (CIPs). In some cases, the CIPs include a first moiety having specific binding for a BTB domain-containing protein or a transcriptional repressor expressed in B cell subpopulations and a second moiety having specific binding for a modulator of gene regulation. In some cases, the BTB domain-containing protein comprises BCL6. In some cases, the transcriptional repressor expressed in B cell subpopulations is PRDM1 or IRF4. In some cases the modulator of gene regulation comprises BRD4, CDK9, and / or p300.

The purpose of the present invention is to provide a compound that has an excellent effect of inducing BRD4 protein degradation and is useful as a cancer therapeutic agent, or a pharmaceutically acceptable salt thereof. A compound represented by formula (I) or a pharmaceutically acceptable salt thereof. [In the formula, each symbol is as defined in the description.]

The application discloses a phthalocyanine-based photo-PROTAC drug and a preparation method and application thereof, and mainly adopts a chemical synthesis method of amino and carboxyl coupling, takes photosensitizer ZnPc and BRD4 ligand JQ1 (a BRD4 inhibitor) as a structural main body, selects a polyethylene glycol (PEG) chain with different lengths as a linker of ZnPc and JQ1, and constructs a photo-PROTAC drug with BRD4 as a target point. The raw material of the application has a wide source, and the preparation method is simple. The drug utilizes the expression of BRD4 in bladder cancer tumor tissues, and realizes efficient degradation of PROTAC independent of E3 ubiquitinase by combining selective tumor site light. Meanwhile, BRD4 degradation destroys the antioxidant and hypoxic inhibition barrier of PDT, and realizes synergistic effect of PDT and PROTAC.

Provided in the present invention are a heterobifunctional compound for targeted degradation of BRD4 based on HSP70, preparation, and use, belonging to the technical fields of pharmaceutical synthesis and chemical engineering. In the present application, an HSP70 inhibitor is selected as a ligand moiety A that binds to HSP70, a BRD4 inhibitor is selected as a ligand moiety B that binds to BRD4, and the ligand A of HSP70 and the ligand B of BRD4 are linked by means of a linking chain, Linker, to obtain a series of bifunctional degradation agents that can degrade BRD4 to different degrees. The obtained degradation agents have the characteristics of high selectivity and strong activity, and can overcome the disadvantages of BRD4 inhibitors, such as poor selectivity for tumor tissues and strong toxic and side effects.

The present disclosure provides a use of a substance targeting BRD4 in the preparation of a product related to diabetes. In the present disclosure, it is found that the expression of BRD4 in human diabetic beta cells is significantly reduced, and BRD4 plays an important role in maintaining beta cell maturation and differentiation, and long-term and acute BRD4 deficiency can lead to reduced insulin secretion and down-regulation of differentiation markers, highlighting the key role of BRD4 in pancreatic beta cells, providing a target BRD4 that has a significant impact on diabetes, so that substances targeting BRD4 can help to assess the susceptibility of diabetes, screening, prevention, intervention and treatment of diabetes.

Disclosed in the present invention are a compound having a BRD4 inhibitory activity, a preparation method therefor and the use thereof. The structure of the compound having the BRD4 inhibitory activity of the present invention is as shown in formula I, and the definition of each substituent is as described in the description and claims. The compound of the present invention has a high bromodomain protein inhibitory activity, in particular a BRD4-targeting inhibitory activity, and can be used for the treatment and / or prevention of related diseases mediated by bromodomain proteins.

The application relates to the technical field of pharmaceutical chemistry, in particular to a kind of azaphen compounds with BRD4 protein inhibition effect and preparation method and application thereof, these compounds can inhibit the interaction between BRD4 and p53 tumor suppressor, can be used for preparing BRD4 protein inhibitor, for preventing and treating the disease related to BRD4 protein inhibitor, good anti-tumor activity, with wide application prospect, structural formula is as shown in formula (I): wherein R1 is selected from hydrogen or methoxy;R2 is selected from hydrogen, methoxy or dimethylamino;R3 is selected from hydrogen or methoxy;R4 is selected from hydrogen or alkyl;R5 is selected from substituted benzene ring or naphthalene.

The application discloses a molecular marker and a kit for assisting in diagnosing cancer. The application provides application of a substance for detecting a BRD4 gene methylation level in preparation of a product; the product is used in at least one of the following aspects: assisting in diagnosing cancer or predicting a cancer disease risk; assisting in distinguishing a benign nodule and cancer; assisting in distinguishing different subtypes of cancer; assisting in distinguishing different stages of cancer; assisting in distinguishing different cancers; determining whether a to-be-detected substance hinders or promotes occurrence of cancer; and the cancer can be lung cancer or breast cancer. The application finds a low methylation phenomenon of the BRD4 gene in blood of lung cancer and breast cancer patients, and has important scientific significance and clinical application value for improving early diagnosis and treatment effect of lung cancer and breast cancer and reducing a death rate.

Provided herein are methods of treating cancer using a combination of a compound provided herein (e.g., Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, or Compound 7, or a stereoisomer or mixture of stereoisomers, a pharmaceutically acceptable salt, a tautomer, a prodrug, a solvate, a hydrate, a co-crystal, a clathrate, or a polymorph thereof) and a second active agent. The second active agent is one or more of a PLK1 inhibitor, a BRD4 inhibitor, a BET inhibitor, a NEK2 inhibitor, a AURKB inhibitor, a MEK inhibitor, a PHF19 inhibitor, a BTK inhibitor, a mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BIRC5 inhibitor, or a DNA methyltransferase inhibitor.

The application discloses a method for detecting aortic dissection based on peripheral blood BRD4 by using flow cytometry and application thereof. The application belongs to the technical field of biology and particularly relates to a method for detecting aortic dissection based on peripheral blood BRD4 by using flow cytometry and application thereof. The method for detecting the content or expression level of bromodomain-containing protein 4 in a to-be-detected sample established by the application comprises the following steps: 1) processing a to-be-detected sample to obtain single nucleus cells; 2) determining a fluorescein-coupled antibody composition of a detection index according to a flow cytometry color matching scheme; 3) mixing the single nucleus cells in step 1) and the fluorescein-coupled antibody in step 2) uniformly, and performing staining by incubation in the dark; 4) performing sample testing on a spectrum flow cytometer; and 5) performing data result analysis. The detection index in step 2) is CD45, CD11B, CD66B, CD14, CC16 and BRD4.

The application discloses a triazolopyridine bromodomain-containing protein 4 (BRD4) small molecule inhibitor and a preparation method and application thereof, a compound or a pharmaceutically acceptable salt or a racemate thereof, the general formula of which is shown as formula (I). The novel synthetic triazolopyridine compound effectively regulates the occurrence and development process of related diseases by inhibiting the activity of BRD4 protein. In addition to the advantage of inhibiting the activity of BRD4 protein, the compound has good water solubility and liver microsomal stability, which means that it can be better absorbed and distributed in the body, thereby improving the therapeutic effect. The compound also has good drugability, so that it can be better applied to various inflammatory, autoimmune diseases and tumor drugs. The application provides a new choice for the treatment of related diseases and is expected to play an important role in clinical practice.

The invention provides heterobifunctional compounds which may bind to both an androgen receptor and BRD4 (bromodomain-containing protein 4). Also provided are pharmaceutical compositions comprising the same and their use in treating disease, CN such as cancer.

The invention provides heterobifunctional compounds which may bind to both an androgen receptor and BRD4 (bromodomain-containing protein 4). Also provided are pharmaceutical compositions comprising the same and their use in treating disease, CN such as cancer.

The purpose of the present invention is to provide a compound that has an excellent effect of inducing BRD4 protein degradation and is useful as a cancer therapeutic agent, or a pharmaceutically acceptable salt thereof. A compound represented by formula (I) or a pharmaceutically acceptable salt thereof. [In the formula, each symbol is as defined in the description.]

Methods and compositions for treating, inhibiting, and / or preventing diseases or disorders associated with aberrant bromodomain-containing protein 4 (BRD4) and phosphoinositide 3-kinase (PBK) activity are disclosed, the methods comprise contacting a solution, cell, tissue, or subject expressing BRD4 and PBK with a compound having Benzopyran-4-One core.

The invention relates to the technical field of tumor treatment, in particular to a VEGFR-2 / BRD4 double-target inhibitor and application thereof. The structural general formula of the VEGFR-2 / BRD4 double-target inhibitor is as shown in a formula I in the specification. The tetrahydropteridine compound containing the aryl amide or aryl urea structure, disclosed by the invention, has relatively strong inhibitory activity on VEGFR-2 / BRD4 activity; according to the present invention, the VEGFR-2 / BRD4 double-target inhibitor has good anti-proliferative activity on tumor cells, the compound I-5 shows the optimal activity, and the activity is far superior to the positive control Sorafenib, ReGrafenib and JQ-1, the effect of the ReGrafenib and the effect of the combination of the Sorafenib and the JQ-1 respectively, and the target treatment drug for leukemia, gastrointestinal stromal tumor, liver cancer, kidney cancer, thyroid cancer, non-small cell lung cancer, colorectal cancer and the like can be prepared, and the compound I-5 can be used for the preparation of the target treatment drug for treating leukemia, gastrointestinal stromal tumor, liver cancer, kidney cancer, thyroid cancer, non-small cell lung cancer, colorectal cancer and the like.

The application provides application of an agent for inhibiting TCF19 in preparation of a drug for treating lung adenocarcinoma, and belongs to the technical field of biological medicine. The application research finds that TCF19 is significantly highly expressed in lung adenocarcinoma tissues; knocking down TCF19 can inhibit lung adenocarcinoma proliferation and can enhance the chemotherapeutic effect of 5-fluorouracil; meanwhile, it is found that the upstream regulatory factor of TCF19 which is regulated and expressed to be increased by lung adenocarcinoma is BRD4, and when BRD4 is knocked down, the mRNA level of TCF19 is obviously reduced, and the protein level is also obviously reduced. TCF19 can be used as a therapeutic target of lung adenocarcinoma, and the agent for inhibiting TCF19 is used for preparing the drug for treating lung adenocarcinoma, and has very high application prospect and medical value.

The present application relates to crystalline solid forms of an inhibitor of BET proteins such as BRD2, BRD3, BRD4, and BRD-t, including methods of preparation thereof, and intermediates in the preparation thereof, where the compound is useful in the treatment of diseases such as cancer.

A self-assembled therapeutic dendron-micelle includes a first amphiphilic dendron-coil, a second amphiphilic dendron-coil, and optionally a third amphiphilic dendron-coil, and an encapsulated BRD4 ligand or BRD4 proteolysis targeting chimera. The first and optional third amphiphilic dendron-coils have a therapeutic peptide conjugated thereto. Also included are pharmaceutical compositions containing the dendron-micelles, methods of making the dendron-micelles, and therapeutic methods including administering the dendron-micelles to a subject in need thereof.

This invention discloses a CDK8 / BRD4 dual-target inhibitor, its preparation method, pharmaceutical composition, and applications, relating to the field of medicinal chemistry. The multi-target inhibitory compound designed and synthesized in this invention can effectively inhibit BET and kinase protein activity. The preferred compound has an IC50 value of [missing information]. 50 The concentration can reach nanomolar levels and has excellent anti-proliferative activity against colorectal cancer cells, achieving excellent therapeutic effects at the molecular level, with a very wide range of application prospects; at the same time, the compound preparation method provided by this invention is highly versatile and suitable for various structural types.

The invention discloses a benzimidazole compound as well as a preparation method, a pharmaceutical composition and application thereof. The structure of the compound is shown as a formula A. The compound not only has good selectivity on HDAC6 / BRD4 protein, but also has a good inhibition effect on fat cells, and has wide application prospects in the aspect of treating and / or preventing various diseases related to HDAC6 / BRD4 activity inhibition. Meanwhile, the preparation method of the compound is convenient, efficient, high in universality and easy in structure expansion. A.