KD36 is a selective KRAS-G12C inhibitor with an IC50 value of 0.92 μM. It suppresses the phosphorylation of ERK and AKT, induces the accumulation of reactive oxygen species (ROS), and reduces mitochondrial membrane potential, leading to apoptosis in KRAS-G12C mutant cells. KD36 is applicable in research related to non-small cell lung cancer (NSCLC).

KRas (G12C):0.92 μM

KD36 exhibits significant anti-proliferative activity in KRAS-G12C mutant NCI-H23 and NCI-H358 cells, with IC 50 values of 0.42 and 0.65 μM, respectively. KD36, at concentrations of 0.5-4.0 μM for 24-48 hours, induces mitochondrial-dependent apoptosis by increasing ROS levels and decreasing mitochondrial membrane potential in NCI-H23 cells. At 0.5-8.0 μM for 8 hours, KD36 significantly inhibits the phosphorylation of ERK and AKT (p-ERK, p-AKT), which are downstream effectors of KRAS, in NCI-H23 cells, while showing no notable inhibitory effect on KRAS wild-type NCI-H2228 cells. Additionally, at concentrations of 0.1-1.0 μM over 14 days, KD36 inhibits colony formation in a dose-dependent manner in both NCI-H23 and NCI-H358 cells.

KD36, administered intraperitoneally at 30 mg/kg once daily for 11 days, significantly inhibits tumor growth in NCI-H358 xenograft model mice, achieving a tumor growth inhibition rate (TGI) of 54.6%.