KRAS inhibitor-9, a potent KRAS inhibitor (Kd=92 μM), blocks the formation of GTP-KRAS and downstream activation of KRAS. KRAS inhibitor-9 binds to KRAS G12D, KRAS G12C and KRAS Q61H protein with a moderate binding affinity. KRAS inhibitor-9 causes G2/M cell cycle arrest and induces apoptosis. KRAS inhibitor-9 selectively inhibits the proliferation of NSCLC cells with KRAS mutation but not normal lung cells[1].
KRAS inhibitor-9 bound to KRASG12D, KRAS G12C and KRAS Q61H protein with a moderate binding affinity of -5.38, -5.41, and -3.97 kcal/mol, respectively[1]. KRAS inhibitor-9 (0-100 μM) shows strong inhibition selectivity in NSCLC cells with IC50s ranging from 39.56 to 66.02 μM for H2122, H358 and H460 cells (at 72 hours)[1].KRAS inhibitor-9 (0-100 μM; 24 hours) blocks GTP-KRAS formation in H2122, H358 and H460 cells[1].KRAS inhibitor-9 (25-100 μM; 48 hours) inhibits the activation of KRAS downstream signaling pathway[1].KRAS inhibitor-9 (0-100 μM; 24-72 hours) induces cell cycle arrest and apoptosis in NSCLC[1]. Cell Viability Assay[1] Cell Line: H2122 (KRAS G12C), H358 (KRAS G12C) and H460 (KRAS Q61H) cell lines
[1]. Xie C, et al. Identification of a New Potent Inhibitor Targeting KRAS in Non-small Cell Lung Cancer Cells. Front Pharmacol. 2017;8:823. Published 2017 Nov 14.