9D11

Smarca2 Bromodomain in complex with compound 22

これはPDB形式変換不可エントリーです。

9D11 の概要

• エントリーDOI: 10.2210/pdb9d11/pdb
• 分子名称: Isoform Short of Probable global transcription activator SNF2L2, ZINC ION, (12'S)-4'-chloro-10'-(piperidin-4-yl)-5'H-spiro[cyclohexane-1,7'-indolo[1,2-a]quinazolin]-5'-one, ... (6 entities in total)
• 機能のキーワード: smarca2, brm, swi/snf, bromodomain, 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: 45122.98

構造登録者

Meagher, J.L.,Stuckey, J.A. (登録日: 2024-08-07, 公開日: 2025-01-15, 最終更新日: 2025-02-05)

主引用文献

Leng, L.,Tu, W.,Yang, L.,Huang, L.,Wang, M.,Meagher, J.L.,Chinnaswamy, K.,Allu, S.R.,Rej, R.K.,Tosovic, J.,Harikrishnan, L.,Li, Z.,Sui, Z.,Stuckey, J.A.,Wang, S.
Discovery of High-Affinity SMARCA2/4 Bromodomain Ligands and Development of Potent and Exceptionally Selective SMARCA2 PROTAC Degraders.
J.Med.Chem., 68:1113-1133, 2025

PubMed Abstract: In the SWI/SNF chromatin-remodeling complex, the mutually exclusive catalytic ATPase subunits SMARCA2 and SMARCA4 proteins have a synthetic-lethal relationship. Selectively targeting SMARCA2 for degradation is a promising and new therapeutic strategy for human cancers harboring inactivated mutated SMARCA4. In this study, we report the design, synthesis, and biological evaluation of novel SMARCA2/4 ligands and our subsequent design of PROTAC degraders using high-affinity SMARCA ligands and VHL-1 ligands. Our efforts led to the discovery of high-affinity SMARCA2/4 bromodomain ligands and the development of a potent and selective SMARCA2 degrader and a highly potent SMARCA2/4 and PBRM1 degrader.

PubMed: 39745064
DOI: 10.1021/acs.jmedchem.4c01903

実験手法

X-RAY DIFFRACTION (1.684 Å)