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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