Friday, April 10, 2020

Targeted Degradation of Oncogenic KRASG12C by VHL-recruiting PROTACs [@CraigMCrews]

Bond, Michael J.; Chu, Ling; Nalawansha, Dhanusha A.; Li, Ke; Crews, Craig

ChemRxiv, 2020

We report the development of LC-2, the first PROTAC capable of degrading endogenous KRASG12C. LC-2 covalently binds KRASG12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRASG12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRASG12C cell lines. LC-2 demonstrates that PROTAC-mediated degradation is a viable option for attenuating oncogenic KRAS levels and downstream signaling in cancer cells.

Covalent drug discovery using sulfur(VI) fluoride exchange warheads

Huang Huang, Lyn H. Jones Expert Opinion on Drug Discovery , 2023 Covalent drug discovery has ...