LC-2

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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 DC50s 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.

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.Western Blot Analysis Cell Line:MIA PaCa-2 cells and NCI-H23 cells Concentration:2.5 μM Incubation Time:6-24 hours Result:Inhibition and degradation of KRAS G12C decreases pErk signaling at 6 and 24 h in homozygous MIA PaCa-2 cells

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Others

Other Targets

PROTACs

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2502156-03-6

1132.78

C59H71ClFN11O7S

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 50 mg/mL (44.14 mM; 超声助溶 (<80°C)

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

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(-20℃)

With Ice Pack

≥ 2 years