Authors: James Bennett, Oleg Fedorov, Cynthia Tallant, Octovia Monteiro, Julia Meier, Vicky Gamble, Pavel Savitsky, Graciela A. Nunez-Alonso, Bernard Haendler, Catherine Rogers, Paul E. Brennan, Susanne Müller, Stefan Knapp

作者： James Bennett, Oleg Fedorov, Cynthia Tallant, Octovia Monteiro, Julia Meier, Vicky Gamble, Pavel Savitsky, Graciela A. Nunez-Alonso, Bernard Haendler, Catherine Rogers, Paul E. Brennan, Susanne Müller, Stefan Knapp

Journal: Journal of Medicinal Chemistry

期刊： 药物化学杂志

Publication Date: February 25, 2016

出版日期： 2016年2月25日

Volume: 59   Pages: 1642-1647

卷： 59    页码： 1642-1647

DOI: 10.1021/acs.jmedchem.5b00458

Summary:

The study by Bennett et al. describes the development and characterization of a novel chemical inhibitor that selectively targets the bromodomains of TRIM24 and BRPF. TRIM24 is known to be a transcriptional regulator and an E3 ubiquitin ligase, often overexpressed in various tumors, correlating with poor prognosis in breast cancer patients. The research focuses on identifying potent benzimidazolone inhibitors that mimic acetyl-lysine to inhibit TRIM24 bromodomains effectively. The most promising compound from this series shows high selectivity and binding affinity to TRIM24 and BRPF1B bromodomains, with dissociation constants (K_D) of 137 nM and 222 nM, respectively. The study demonstrates cellular activity of the inhibitor through Fluorescence Recovery After Photobleaching (FRAP) assays and cell viability tests, suggesting its potential as a therapeutic tool.

摘要：

Bennett等人的研究描述了一种新型化学抑制剂的开发和特征，该抑制剂专门靶向TRIM24和BRPF的溴结构域。TRIM24被认为是一种转录调节因子和E3泛素连接酶，常在各种肿瘤中过度表达，并与乳腺癌患者的不良预后相关。该研究主要集中在识别有效的苯并咪唑酮抑制剂，这些抑制剂模仿乙酰赖氨酸以有效地抑制TRIM24的溴结构域。该系列中最有前途的化合物表现出对TRIM24和BRPF1B溴结构域的高选择性和结合亲和力，其解离常数（K_D）分别为137 nM和222 nM。研究通过荧光漂白恢复（FRAP）试验和细胞活力测试证明了该抑制剂的细胞活性，表明其作为治疗工具的潜力。

Here are a few compounds related to TRIM24 bromodomain inhibitors along with their corresponding CAS numbers:

1.IACS-9571

CAS Number: 1800477-30-8

Description: A potent and selective inhibitor of TRIM24 and BRPF1 with IC50 of 8 nM for TRIM24.

2.dTRIM24

CAS Number: 2170695-14-2

Description: A potent TRIM24 bromodomain inhibitor with an IC50 of 217.8 nM.