AZD1208

Biochem/physiol Actions

AZD1208 is an orally available, potent ATP-competitive pan-Pim kinase inhibitor (Pim-1/-2/-3 Ki = 0.1/1.92/0.4 nM; Pim-1/-2/-3 IC₅₀ = 0.4/5.0/1.9 nM with [ATP] = Km; Pim-1/-2/-3 IC₅₀ = 2.6/164/17 nM with [ATP] = 5 mM) wtih high target selectivity (by binding assay with a 442-kinase panel). AZD1208 exhibits selective antiproliferation potency against high Pim-1/-2-expressing AML cultures (GI50 in 72 h = 20 nM/MOLM-16, 60 nM/EOL-1, 300 nM/Kasumi-3, 600 nM/KG-1a, 900 nM/MV4-11) and displays in vivo efficacy against MOLM-16 xenograft tumor growth in mice (by 89% or 100%, respectively, with 10 or 30 mg/kg/day p.o.)