2502156-03-6

LC-2 is a von Hippel-Lindau-based PROTAC which can degrade endogenous KRAS G12C. It covalently binds KRAS G12C with a MARTX849 warhead and recruits the E3 ligase VHL which degrades the KRAS G12C and suppresses MAPK signaling in homozygous and heterzygous KRAS G12C cell lines.

LC-2 is a potent and first-in-class von Hippel-Lindau-based PROTAC capable of degrading endogenous KRAS G12C, with DC50s between 0.25 and 0.76 μM[1]. LC-2 covalently binds KRAS G12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRAS G12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRAS G12C cell lines[2].

KRAS(G12C): 0.25-0.76 μM (DC₅₀); VHL

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[1] De Vita E, et al. The Missing Link between (Un)druggable and Degradable KRAS. ACS Cent Sci. 2020;6(8):1281-1284. DOI:10.1021/acscentsci.0c00920
[2] Bond MJ, et al. Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs. ACS Cent Sci. 2020;6(8):1367-1375. DOI:10.1021/acscentsci.0c00411