LC-2 是首创的基于von Hippel-Lindau的内源性 KRAS G12C 的 PROTAC 降解剂，DC₅₀ 在 0.25 和 0.76 μM 之间。LC-2 是一种 PROTAC，与 MRTX849 共价结合 KRAS G12C 并招募 E3 连接酶 VHL，诱导 KRAS G12C 快速持续降解，导致纯合和杂合子 KRAS G12C 细胞系 MAPK 信号的抑制。

LC-2 is a potent and first-in-class von Hippel-Lindau-based PROTAC capable of degrading endogenous KRAS G12C, with DC 50 s between 0.25 and 0.76 μM. 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.

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KRAS(G12C) 0.25-0.76 μM (DC50) VHL pan> pa

LC-2 induces degradation of endogenous KRASG12C in multiple KRAS mutant cancer cell (NCI-H2030, MIA PaCa-2, SW1573, NCI-H23 and NCI-H358 cells) with DC50s between 0.25 and 0.76 μM. LC-2-induced KRASG12C degradation occurs via a bona fide PROTAC mechanism. MIA PaCa-2, NCI-H23, and SW1573 cells are treated with 2.5 μM of LC-2 for 6, 24, 48, and 72 h. In all three cell lines, maximal KRAS degradation occurred within 24 h and was sustained up to 72 h.
LC-2-induced (2.5 μM; 6-24 hours) KRAS G12C degradation modulates Erk signaling in homozygous and heterozygous KRAS mutant cell lines. has not independently confirmed the accuracy of these methods. They are for reference only.

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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.
[2]. Bond MJ, et al. Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs. ACS Cent Sci. 2020;6(8):1367-1375.

In Vitro: DMSO : 50 mg/mL (44.14 mM; ultrasonic and warming and heat to 80°C)配制储备液