6N2J

Tetrahydropyridopyrimidines as Covalent Inhibitors of KRAS-G12C

6N2J の概要

• エントリーDOI: 10.2210/pdb6n2j/pdb
• 分子名称: GTPase KRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: kras proto-oncogene, gtpase, oncoprotein
• 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: 20221.80

構造登録者

Vigers, G.P. (登録日: 2018-11-13, 公開日: 2018-12-12, 最終更新日: 2024-11-06)

主引用文献

Fell, J.B.,Fischer, J.P.,Baer, B.R.,Ballard, J.,Blake, J.F.,Bouhana, K.,Brandhuber, B.J.,Briere, D.M.,Burgess, L.E.,Burkard, M.R.,Chiang, H.,Chicarelli, M.J.,Davidson, K.,Gaudino, J.J.,Hallin, J.,Hanson, L.,Hee, K.,Hicken, E.J.,Hinklin, R.J.,Marx, M.A.,Mejia, M.J.,Olson, P.,Savechenkov, P.,Sudhakar, N.,Tang, T.P.,Vigers, G.P.,Zecca, H.,Christensen, J.G.
Discovery of Tetrahydropyridopyrimidines as Irreversible Covalent Inhibitors of KRAS-G12C with In Vivo Activity.
ACS Med Chem Lett, 9:1230-1234, 2018

PubMed Abstract: is the most frequently mutated driver oncogene in human cancer, and KRAS mutations are commonly associated with poor prognosis and resistance to standard treatment. The ability to effectively target and block the function of mutated KRAS has remained elusive despite decades of research. Recent findings have demonstrated that directly targeting KRAS-G12C with electrophilic small molecules that covalently modify the mutated codon 12 cysteine is feasible. We have discovered a series of tetrahydropyridopyrimidines as irreversible covalent inhibitors of KRAS-G12C with in vivo activity. The PK/PD and efficacy of compound will be highlighted.

PubMed: 30613331
DOI: 10.1021/acsmedchemlett.8b00382

実験手法

X-RAY DIFFRACTION (1.8 Å)