9RTI

Structure of WRN in complex with ATPgS and covalent ligand Compound 7

これはPDB形式変換不可エントリーです。

9RTI の概要

• エントリーDOI: 10.2210/pdb9rti/pdb
• 分子名称: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, DIMETHYL SULFOXIDE, ... (10 entities in total)
• 機能のキーワード: dna damage repair, inhibitor, complex, helicase, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51558.38

構造登録者

Fletcher, C.T.,Rucktooa, P. (登録日: 2025-07-02, 公開日: 2025-10-22, 最終更新日: 2025-11-05)

主引用文献

Smith, G.M.T.,Aithani, L.,Barrett, C.E.,Bucher, A.O.,Cooper, C.D.O.,Degorce, S.L.,Dore, A.S.,Fletcher, C.T.,Huber, S.,Huckvale, R.,Kennedy, A.J.,Mornement, A.A.,Pickworth, M.,Rucktooa, P.,Scully, C.C.G.,Skerratt, S.E.
AI-assisted delivery of novel covalent WRN inhibitors from a non-covalent fragment screen.
Bioorg.Med.Chem.Lett., 131:130421-130421, 2025

PubMed Abstract: Werner (WRN) helicase, has emerged as a promising therapeutic target for cancers associated with microsatellite instability (MSI). This letter describes the discovery of small molecule inhibitors from a fragment screen that occupy a cryptic, allosteric site of WRN helicase. Key findings include the identification of benzimidazole and amino-indazole scaffolds, exploiting their proximity to Cys727 via covalent modification. The use of our proprietary co-folding model DragonFold assisted the identification of novel WRN helicase inhibitors. These, together with near-neighbor profiling, offer tools for furthering the understanding of WRN and BLM helicase function, and potential therapeutic avenues for MSI-associated cancers.

PubMed: 41038585
DOI: 10.1016/j.bmcl.2025.130421

実験手法

X-RAY DIFFRACTION (2.197 Å)