BRD4 inhibitors(Shanghai Institute of Materia Medica Chinese Academy of Sci)(BRD4 inhibitors(Shanghai Institute of Materia Medica Chinese Academy of Sci))

概要

基本信息

药物类型

小分子化药

别名

Compound 23(Shanghai Institute of Materia Medica Chinese Academy of Sci)

靶点

BRD4

作用方式

抑制剂

作用机制

BRD4抑制剂(溴结构域蛋白-4抑制剂)

治疗领域

遗传病与畸形泌尿生殖系统疾病其他疾病

在研适应症

常染色体显性多囊肾病

非在研适应症-

原研机构

中国科学院上海药物研究所

在研机构

中国科学院上海药物研究所

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)临床前

特殊审评-

结构/序列

分子式C27H32N8O

InChIKeyDNRQEQIMNNTGGF-QGZVFWFLSA-N

CAS号2994635-04-8

关联

100 项与 BRD4 inhibitors(Shanghai Institute of Materia Medica Chinese Academy of Sci) 相关的临床结果

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100 项与 BRD4 inhibitors(Shanghai Institute of Materia Medica Chinese Academy of Sci) 相关的转化医学

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100 项与 BRD4 inhibitors(Shanghai Institute of Materia Medica Chinese Academy of Sci) 相关的专利（医药）

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188

项与 BRD4 inhibitors(Shanghai Institute of Materia Medica Chinese Academy of Sci) 相关的文献（医药）

2025-06-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of dual CDK4/6 and BRD4 inhibitor as apoptosis and autophagy inducers against NSCLC in vitro and in vivo

Article

作者: Luo, Zhongwen ; Zheng, Long ; Ma, Liangliang ; Zou, Meiting ; Zhang, Yonglei ; Zheng, Yiwei ; Kong, Lingyi ; Jiang, Yuhan ; Wang, Xiaobing

Target of cyclin dependent kinase (CDK) by inhibitors has demonstrated promising potential as a therapeutic agent for cancer. However, the efficacy of monotherapy on tumors is limited and there is an urgent need for combination therapy with other inhibitors. It has been reported that restoring bromodomain-containing protein 4 (BRD4) resensitivity to tumor cells by inhibiting CDK4/6 is a potential therapeutic strategy. In this study, we present the design and optimization of dual CDK4/6 and BRD4 inhibitors, among which B15 exhibited potent and selective inhibition of both targets in vitro, and significant antiproliferative effects in non-small cell lung cancer (NSCLC) cells. Importantly, it also showed good pharmacokinetic properties in rats, meanwhile, B15 effectively inhibited tumor growth in vivo (TGI = 85.3 %) without causing significant toxicity. Overall, our results introduce a promising strategy of dual CDK4/6 and BRD4 inhibitors for the treatment of NSCLC.

2025-06-01·PHARMACOLOGICAL RESEARCH

Age-linked DNA methylation and gene expression patterns in parameningeal head and neck alveolar rhabdomyosarcoma reveal CDK9 as a promising therapeutic target

Article

作者: Di Giannatale, Angela ; Alaggio, Rita ; Miele, Evelina ; Cassandri, Matteo ; Russo, Ida ; Barresi, Sabina ; Vallese, Silvia ; Pedace, Lucia ; Locatelli, Franco ; Abballe, Luana ; Vinciarelli, Flavia ; Mancini, Barbara ; Patrizi, Sara ; Stracuzzi, Alessandra ; Rota, Rossella ; Antonacci, Celeste ; Giovannoni, Isabella ; Milano, Giuseppe Maria

BACKGROUND:

Alveolar rhabdomyosarcoma (ARMS) primarily affects children in the first decade of life, but it can also occur during adolescence, typically with a more favorable prognosis. This study aimed to explore differences in DNA methylation (DNAm) and gene expression profiles that may account for the worse prognosis in younger patients; and to investigate possible new therapeutic targets.

METHODS:

We conducted whole-genome DNAm and transcriptome analyses on 10 parameningeal head and neck ARMS patients, including 4 patients under 1 year old and 6 over 10 years old. Among the differentially expressed genes, we focused on actionable therapeutic targets and confirmed their protein expression levels by immunohistochemistry. We validated the biological relevance of molecules of interest through functional experiments on rhabdomyosarcoma cell lines.

RESULTS:

DNAm profiles did not significantly differ across age groups, while gene expression was the primary driver of observed differences. Several enriched pathways characterized younger patients with respect to older ones, including FAS, Integrin, PI3 kinase, and p53 by glucose deprivation. Among actionable molecules, cyclin dependent kinase 9 (CDK9) emerged as a promising therapy target, highly expressed in younger patients. Of note, CDK9 inhibitors specifically inhibit cell growth in bi- and three-dimensional ARMS cellular models, both as a monotherapy and in combination with BRD4 inhibitors.

CONCLUSION:

Despite the small sample size, these findings suggest potential age-related molecular mechanisms and highlight candidate genes for further investigation as novel therapeutic targets. Notably, we identified CDK9 as a promising target, warranting further exploration in the context of ARMS treatment.

2025-04-03·EXPERT OPINION ON THERAPEUTIC PATENTS

A patent review of BRD4 inhibitors (2020–present)

Review

作者: Zhou, Huanmin ; Ding, Hong ; Gao, Jing ; Luo, Cheng ; Xue, Shengyu ; Lin, Hua ; Yu, Jiamin ; Chen, Yanfang

INTRODUCTION:

Bromodomain-containing protein 4 (BRD4) stands as a pivotal member within the Bromodomain and Extra-Terminal Domain (BET) family, contributing significantly to epigenetic control and gene expression. Given its association with various cancers, BRD4 emerges as a promising therapeutic target, suggesting a substantial role in the treatment of diverse pathological conditions.

AREAS COVERED:

The present review is centered on patent applications concerning inhibitors targeting BRD4's bromodomain site, published from 2020 to present. A comprehensive evaluation was conducted on a total of 70 applications. The latest patented studies of BRD4 are summarized by using the keywords 'BRD4' in SciFinder, PubMed, and The lens Patents and databases in the year from 2020 to present.

EXPERT OPINION:

Despite the substantial progress achieved in the clinical research of numerous BET bromodomain inhibitors, their development remains fraught with challenges. To mitigate the dose-limiting toxicity (DLT) and other clinical adverse effects associated with pan-BET inhibitors, current research efforts are increasingly focus on the development of selective BRD4-BD1 or -BD2 inhibitors. These selective inhibitors exhibit considerable potential as more efficacious candidate drugs, thereby paving the way for novel avenues in both fundamental and translational research within this domain.

100 项与 BRD4 inhibitors(Shanghai Institute of Materia Medica Chinese Academy of Sci) 相关的药物交易

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