EGFR-IN-197

EGFR-IN-197 is an EGFR inhibitor with IC50 values of 19.5 nM for EGFRL858R/T790M and 12.0 nM for EGFRL858R/T790M/C797S. It arrests the cell cycle of NCI-H1975 cells at the G2/M phase while inhibiting their proliferation, colony formation, and migration. Additionally, it prevents mitochondrial translocation and elevates mitochondrial H2S levels. EGFR-IN-197 disrupts anti-apoptotic signaling by modulating apoptosis-related proteins, induces DNA damage, and activates pro-apoptotic pathways leading to apoptosis (apoptosis). This compound is applicable for research related to non-small cell lung cancer (NSCLC).

EGFR-IN-197 (compound 6e) effectively inhibits the proliferation of NCI-H1975, HCC827, and A431 cells with IC 50 values of 0.0473 μM, 0.0185 μM, and 0.0226 μM, respectively. It also significantly inhibits EGFR L858R/T790M and EGFR L858R/T790M/C797S mutant kinases, with IC 50 values of 19.5 nM and 12.0 nM. EGFR-IN-197 (0.05-0.5 μM; 14 days) suppresses colony formation in NCI-H1975 cells in a concentration-dependent manner. It inhibits cell migration of NCI-H1975 cells concentration-dependently at doses of 0.05-0.5 μM over 24 hours. EGFR-IN-197 disrupts mitochondrial translocation of EGFR in NCI-H1975 cells within the concentration range of 0.05-0.5 μM and also upregulates mitochondrial H₂S levels in a dose-dependent fashion. Phosphorylation of EGFR and ERK1/2 in NCI-H1975 cells is inhibited by EGFR-IN-197 (0.005-0.5 μM; 24 hours), with significant inhibition of AKT phosphorylation at 0.5 μM. Additionally, it modulates apoptosis-related protein expression, increasing Cleaved PARP and Cleaved caspase-3 levels while decreasing Bcl-xL levels. EGFR-IN-197 (0.1-1 μM; 24 hours) induces apoptosis in NCI-H1975 cells in a concentration-dependent manner, strongly inducing late apoptosis at concentrations of 0.5 μM and above. Furthermore, it causes NCI-H1975 cells to arrest in the G2/M phase in a concentration-dependent manner, with 62.29% of cells in the G2/M phase at 0.5 μM. Lastly, EGFR-IN-197 induces DNA damage in NCI-H1975 cells concentration-dependently over 72 hours, with significant damage observed at 0.1 μM and higher concentrations.