LC-2

Description: LC-2 (PROTAC KRASG12C Degrader-LC-2) is a novel von Hippel-Lindau-based PROTAC degrader of endogenous KRAS G12C with a DC50 between 0.25 and 0.76 µM.LC-2 is a PROTAC that covalently binds KRAS G12C with MRTX849 and recruits the E3 ligase, VH, to induce a rapid and sustained degradation of KRAS G12C. LC-2 inhibits MAPK signaling in pure and heterozygous KRAS G12C cell lines. Target: PROTACs. Smiles: Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCOCCCN2CCC[C@H]2COc2nc3CN(CCc3c(n2)N2CCN([C@@H](CC#N)C2)C(=O)C(F)=C)c2cccc3cccc(Cl)c23)C(C)(C)C)cc1. References: De Vita E, et al. The Missing Link between (Un)druggable and Degradable KRAS. ACS Cent Sci. 2020,6(8):1281-1284.