8UC9

SOS2 co-crystal structure with fragment bound (compound 9)

8UC9 の概要

• エントリーDOI: 10.2210/pdb8uc9/pdb
• 分子名称: Son of sevenless homolog 2, 7-chloroquinolin-4-amine (3 entities in total)
• 機能のキーワード: sos2, nucleotide exchange factor, gef, kras, ras, signaling protein, fragment screening, fbld
• 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: 57549.29

構造登録者

Gunn, R.J.,Lawson, J.D. (登録日: 2023-09-26, 公開日: 2024-01-10, 最終更新日: 2024-01-24)

主引用文献

Smith, C.R.,Chen, D.,Christensen, J.G.,Coulombe, R.,Fethiere, J.,Gunn, R.J.,Hollander, J.,Jones, B.,Ketcham, J.M.,Khare, S.,Kuehler, J.,Lawson, J.D.,Marx, M.A.,Olson, P.,Pearson, K.E.,Ren, C.,Tsagris, D.,Ulaganathan, T.,Van't Veer, I.,Wang, X.,Ivetac, A.
Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography.
J.Med.Chem., 67:774-781, 2024

PubMed Abstract: SOS1 and SOS2 are guanine nucleotide exchange factors that mediate RTK-stimulated RAS activation. Selective SOS1:KRAS PPI inhibitors are currently under clinical investigation, whereas there are no reports to date of SOS2:KRAS PPI inhibitors. SOS2 activity is implicated in MAPK rebound when divergent SOS1 mutant cell lines are treated with the SOS1 inhibitor BI-3406; therefore, SOS2:KRAS inhibitors are of therapeutic interest. In this report, we detail a fragment-based screening strategy to identify X-ray cocrystal structures of five diverse fragment hits bound to SOS2.

PubMed: 38156904
DOI: 10.1021/acs.jmedchem.3c02140

実験手法

X-RAY DIFFRACTION (2.44 Å)