9QFF

Structure of SOS1 in complex with compound 3

これはPDB形式変換不可エントリーです。

9QFF の概要

• エントリーDOI: 10.2210/pdb9qff/pdb
• 分子名称: Son of sevenless homolog 1, 3-[[3-(trifluoromethyl)phenyl]methyl]-2~{H}-1$l^{6},2,4-benzothiadiazine 1,1-dioxide (3 entities in total)
• 機能のキーワード: gef, cytosolic protein
• 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: 57716.96

構造登録者

Breed, J. (登録日: 2025-03-11, 公開日: 2025-09-17, 最終更新日: 2025-11-05)

主引用文献

Bonomo, S.,Gibault, F.,Bagal, S.K.,Blackwell, J.H.,Breed, J.,Collie, G.W.,Couturier, M.,Diene, C.,Di Fruscia, P.,Gray, S.,Hughes, C.,Jeyaharan, D.,Kettle, J.G.,Milbradt, A.G.,Northall, S.,Peters, K.,Stubbs, C.J.,Underwood, E.,Chen, Y.,Hao, H.,Lainchbury, M.D.
Focused Structure-Based Virtual Screening Identifies Novel Inhibitors of SOS1.
Acs Med.Chem.Lett., 16:1905-1909, 2025

PubMed Abstract: SOS1 is one of the key regulators of KRAS where it catalyzes the GTP-to-GDP turnover required for KRAS activation. Inhibition of the SOS1::KRAS interaction is an attractive strategy to modulate abnormal KRAS activation, which is responsible for several malignancies. In this work, we performed a virtual screening campaign on the AstraZeneca compound collection with Heavy Atom Count between 21 and 26 and identified two novel and efficient binders of SOS1 which fulfill the minimal pharmacophoric requirements disclosed in known compounds. Subsequently, structure- and knowledge-based approaches were applied to develop these binders into functional inhibitors of SOS1.

PubMed: 41089494
DOI: 10.1021/acsmedchemlett.5c00302

実験手法

X-RAY DIFFRACTION (1.879 Å)