9QAC

Crystal structure of the SMARCA2 bromodomain bound to a fragment screening hit

これはPDB形式変換不可エントリーです。

9QAC の概要

• エントリーDOI: 10.2210/pdb9qac/pdb
• 分子名称: Probable global transcription activator SNF2L2, methyl 2-azanyl-1~{H}-indole-3-carboxylate, ZINC ION, ... (4 entities in total)
• 機能のキーワード: bromodomain, fragment screening hit, gene regulation
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 43908.45

構造登録者

Schimpl, M. (登録日: 2025-02-28, 公開日: 2025-06-18, 最終更新日: 2025-07-02)

主引用文献

Boerth, J.A.,Schimpl, M.,Lucas, S.C.C.,Zhang, J.,Code, E.L.,Embrey, K.J.,Rawlins, P.B.,Wang, H.,Storer, R.I.,Di Fruscia, P.,Nelson, J.E.,Milbradt, A.G.,Borjesson, U.,Gohlke, A.,Korboukh, V.,Gopalsamy, A.
Discovery of Pyrimidoindolones as Novel Family VIII Bromodomain Binders.
Acs Med.Chem.Lett., 16:1073-1079, 2025

PubMed Abstract: Suppression of oncogenic gene expression is an effective strategy for the treatment of cancer. The SWI/SNF (SWItch/Sucrose Non-Fermentable) complex plays an important role in regulating gene activation or repression, and its dysregulation has been linked to aberrant transcription activity in many types of cancer. Targeting the subunits of this complex, such as SMARCA2, SMARCA4, and PBRM1, which are part of the bromodomain family VIII, has significant therapeutic potential. Herein we report the discovery of pyrimidoindolones as a novel series of bromodomain family VIII binders identified through an NMR-based fragment screen. These binders have been optimized to achieve sub-μM affinity for the family VIII proteins SMARCA2, SMARCA4, and PRBM1, with promising physicochemical properties.

PubMed: 40529061
DOI: 10.1021/acsmedchemlett.5c00120

実験手法

X-RAY DIFFRACTION (2.07 Å)