Crystal Structure of Kirsten Rat Sarcoma G12C Complexed with GMPPNP and Covalently Bound to an Adduct of {(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]-1-[(2Z)-2-fluoro-3-(pyridin-2-yl)prop-2-enoyl]piperazin-2-yl}acetonitrile

Crystal Structure of Kirsten Rat Sarcoma G12C Complexed with GMPPNP and Covalently Bound to an Adduct of {(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]-1-[(2Z)-2-fluoro-3-(pyridin-2-yl)prop-2-enoyl]piperazin-2-yl}acetonitrile Descriptor: Isoform 2B of GTPase KRas, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... Authors: Sheriff, S, Pokross, M, Witmer, M. Deposit date: 2025-04-01 Release date: 2025-11-05 Last modified: 2026-03-18 Method: X-RAY DIFFRACTION (1.586 Å) Cite: Covalent inhibitor design confers activity against both GDP- and GTP-bound forms of KRAS G12C. Nat Commun, 17, 2026

结合鸟苷-5'-β,γ-亚甲基三磷酸（GMPPNP）并与{(2S)-4-[7-(8-氯萘-1-基)-2-{[(2S)-1-甲基吡咯烷-2-基]甲氧基}-5,6,7,8-四氢吡啶并[3,4-d]嘧啶-4-基]-1-[(2Z)-2-氟-3-(吡啶-2-基)丙-2-烯酰基]哌嗪-2-基}乙腈加合物共价结合的KRAS G12C晶体结构
成分描述：GTP酶KRAS的2B亚型、镁离子、磷氨基膦酸鸟苷酯等
作者：Sheriff, S、Pokross, M、Witmer, M
提交日期：2025-04-01
发布日期：2025-11-05
最后修改日期：2026-03-18
实验方法：X射线衍射（分辨率1.586 Å）
引用文献：《共价抑制剂设计可实现针对KRAS G12C的GDP结合型与GTP结合型两种形式的活性》，《自然-通讯》（Nat Commun），17卷，2026年