KRCA-0377

KRCA-0377 is an orally active ALK inhibitor with an IC₅₀ of 0.001 μM. KRCA-0377 also inhibits mutant ALK enzyme with IC50 values ≤0.01 μM. KRCA-0377 shows cytotoxicity against cancer cells and inhibits tumor growth in xenograft mice models. KRCA-0377 can be used for the research of ALK-positive non-small-cell lung cancer^[1]. In Vitro:KRCA-0377 (Compound 8) (30 min) potently inhibits wild-type ALK with an IC₅₀ of 0.001 μM and ALK^L1196M mutant enzyme with an IC₅₀ of 0.01 μM^[1].
KRCA-0377 (30 min) potently inhibits multiple Crizotinib (HY-50878)-resistant ALK mutant enzymes, including ALK^G1202R (IC₅₀ = 0.0059 μM), ALK^G1269A (IC₅₀ = 0.0017 μM), ALK^{T1151-L1152 inst T} (IC₅₀ = 0.0023 μM), ALK^F1174L (IC₅₀ = 0.0021 μM), and ALK^C1156Y (IC₅₀ = 0.0030 μM)^[1].
KRCA-0377 (72 h) induces cytotoxicity in ALK-positive H2228 (CC₅₀ = 0.01 μM), H3122 (CC₅₀ = 0.008 μM), and Ba/F3 ALK^L1196M (CC₅₀ = 0.036 μM) cells after 72 h of incubation^[1].
KRCA-0377 (1 μM) inhibits approximately one-third of a panel of 96 kinases by over 90%^[1]. In Vivo:KRCA-0377 (Compound 8) (50 mg/kg; p.o.; daily; 14 days) produces statistically significant inhibition of H3122 xenograft tumor growth in female nude mice^[1].