文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

GNE-064:一种强效、选择性、口服生物可利用的 SMARCA2 和 SMARCA4 溴结构域以及 PBRM1 第五个溴结构域化学探针。

GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1.

机构信息

Constellation, a Morphosys Company, 215 First Street, Suite 200, Cambridge, Massachusetts 02142, United States.

Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.

出版信息

J Med Chem. 2022 Aug 25;65(16):11177-11186. doi: 10.1021/acs.jmedchem.2c00662. Epub 2022 Aug 5.


DOI:10.1021/acs.jmedchem.2c00662
PMID:35930799
Abstract

Bromodomains are acetyllysine recognition domains present in a variety of human proteins. Bromodomains also bind small molecules that compete with acetyllysine, and therefore bromodomains have been targets for drug discovery efforts. Highly potent and selective ligands with good cellular permeability have been proposed as chemical probes for use in exploring the functions of many of the bromodomain proteins. We report here the discovery of a class of such inhibitors targeting the family VIII bromodomains of SMARCA2 (BRM) and SMARCA4 (BRG1), and PBRM1 (polybromo-1) bromodomain 5. We propose one example from this series, GNE-064, as a chemical probe for the bromodomains SMARCA2, SMARCA4, and PBRM1(5) with the potential for use.

摘要

溴结构域是存在于多种人类蛋白质中的乙酰赖氨酸识别结构域。溴结构域还结合与乙酰赖氨酸竞争的小分子,因此溴结构域一直是药物发现努力的目标。具有良好细胞通透性的高活性和选择性配体已被提议用作化学探针,用于探索许多溴结构域蛋白的功能。我们在此报告了一类针对 SMARCA2(BRM)和 SMARCA4(BRG1)家族 VIII 溴结构域以及 PBRM1(多溴-1)溴结构域 5 的抑制剂的发现。我们提出了该系列中的一个例子 GNE-064,作为用于溴结构域 SMARCA2、SMARCA4 和 PBRM1(5)的化学探针,具有潜在的用途。

相似文献

[1]
GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1.

J Med Chem. 2022-8-25

[2]
GNE-235: A Lead Compound Selective for the Second Bromodomain of PBRM1.

J Med Chem. 2023-9-28

[3]
Selective and Cell-Active PBRM1 Bromodomain Inhibitors Discovered through NMR Fragment Screening.

J Med Chem. 2022-10-27

[4]
Cancer-associated polybromo-1 bromodomain 4 missense variants variably impact bromodomain ligand binding and cell growth suppression.

J Biol Chem. 2024-4

[5]
Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis.

J Med Chem. 2020-12-10

[6]
Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex.

J Med Chem. 2016-5-26

[7]
Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type.

J Pathol. 2016-2

[8]
Synthetic lethality: targeting the SMARCA2 bromodomain for degradation in SMARCA4-deficient tumors - a review of patent literature from 2019-June 2023.

Expert Opin Ther Pat. 2024-4

[9]
Residual complexes containing SMARCA2 (BRM) underlie the oncogenic drive of SMARCA4 (BRG1) mutation.

Mol Cell Biol. 2014-1-13

[10]
The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies.

Cancer Res. 2015-9-15

引用本文的文献

[1]
Discovery of Pyrimidoindolones as Novel Family VIII Bromodomain Binders.

ACS Med Chem Lett. 2025-5-8

[2]
Epigenetics-targeted drugs: current paradigms and future challenges.

Signal Transduct Target Ther. 2024-11-26

[3]
Rational Design and Development of Selective BRD7 Bromodomain Inhibitors and Their Activity in Prostate Cancer.

J Med Chem. 2023-8-24

[4]
The pyridazine heterocycle in molecular recognition and drug discovery.

Med Chem Res. 2023-3-15

[5]
Target 2035 - an update on private sector contributions.

RSC Med Chem. 2023-3-16

[6]
Targeting Chromatin-Remodeling Factors in Cancer Cells: Promising Molecules in Cancer Therapy.

Int J Mol Sci. 2022-10-24

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索