EGFR-IN-1

EGFR-IN-1 (compound 24) is an orally active and irreversible L858R/T790M mutant selective EGFR inhibitor. EGFR-IN-1 potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR. EGFR-IN-1 displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity^[1]. In Vitro: EGFR-IN-1 (10 μM; 72 hours) displays strong antiproliferative activity against the H1975 and HCC827 cells with IC50s of 4 and 28 nM, respectively^[1].
EGFR-IN-1 inhibits p-EGFR in H1975 and HCC827 cells with IC₅₀s of 4 and 9 nM, respectively. EGFR-IN-1 highly selective against a panel of 100 kinases^[1]. In Vivo: EGFR-IN-1 (30 mg/kg; p.o.; daily for 2 weeks) displays significant tumor growth inhibition with no observed loss in body weight^[1].
EGFR-IN-1 evaluates in a time course PD experiment upon oral dosing at 30 mg/kg. EGFR-IN-1 shows a >50% inhibition of phosphorylation of EGFR for >12 h. EGFR-IN-1 reaches maximal concentration of 0.10 μM at 2 h and systemic exposure (AUC0-inf.) is 0.33 μM. h^[1].