Quizartinib

Soluble in DMSO. Slightly soluble (<1mg/ml) in ethanol. Quizartinib (AC220) is a second-generation FLT3 inhibitor that has shown promising activity in AML in Phase II clinical trials. It inhibits mutant and wild-type FLT3 in vivo at 0.1 and 0.5µM, respectively, and has shown favorable activity and tolerability in phase I and II trials in acute myeloid leukemia, with QT prolongation as the dose-limiting toxicity. Recently, AC220 has also been shown to be an effective inhibitor of ATP-binding cassette (ABC) proteins ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein). Quizartinib inhibited transport of fluorescent ABCG2 and ABCB1 substrates in ABCG2- and ABCB1-overexpressing cells in a concentration-dependent manner, from 0.1 to 5µM and from 0.5 to 10µM, respectively, and inhibited [125I]-IAAP photolabeling of ABCG2 and ABCB1 with IC(50) values of 0.07 and 3.3µM, respectively. Target: FLT3 , Kinase Group: RTK , Substrate: Tyrosine