Article
Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor.
Cell - 25 Jan 2018
Janes Matthew R, Zhang Jingchuan, Li Lian-Sheng, Hansen Rasmus, Peters Ulf, Guo Xin, Chen Yuching, Babbar Anjali, Firdaus Sarah J, Darjania Levan, Feng Jun, Chen Jeffrey H, Li Shuangwei, Li Shisheng, Long Yun O, Thach Carol, Liu Yuan, Zarieh Ata, Ely Tess, Kucharski Jeff M, Kessler Linda V, Wu Tao, Yu Ke, Wang Yi, Yao Yvonne, Deng Xiaohu, Zarrinkar Patrick P, Brehmer Dirk, Dhanak Dashyant, Lorenzi Matthew V, Hu-Lowe Dana, Patricelli Matthew P, Ren Pingda, Liu Yi
Abstract excerpt
KRASG12C was recently identified to be potentially druggable by allele-specific covalent targeting of Cys-12 in vicinity to an inducible allosteric switch II pocket (S-IIP). Success of this approach requires active cycling of KRASG12C between its active-GTP and inactive-GDP conformations as accessibility of the S-IIP is restricted only to the GDP-bound state. This strategy proved feasible for inhibiting mutant...
Read the complete abstract on PubMedTopics
Share this publication in a Topic to start or enrich a Post.