AC886

AC886 is the major active metabolite of quizartinib (AC220), a potent and selective second-generation type II FLT3 inhibitor developed by Daiichi Sankyo (originally Ambit Biosciences). AC886 is formed in vivo via the O-demethylation of quizartinib, a process primarily mediated by the cytochrome P450 enzyme CYP3A4. Like its parent compound, AC886 acts as a competitive inhibitor of the FMS-like tyrosine kinase 3 (FLT3) receptor, specifically targeting the internal tandem duplication (ITD) mutation. In clinical settings, AC886 circulates at plasma concentrations that are often higher than those of quizartinib and possesses a significantly longer terminal half-life, making it a major contributor to the overall antileukemic activity and the sustained inhibition of FLT3 phosphorylation. It is primarily relevant in the treatment of patients with relapsed or refractory FLT3-ITD-positive acute myeloid leukemia (AML), where its pharmacological profile contributes to both the efficacy and the safety considerations, such as the risk of QTc interval prolongation.

Other names

O-desmethylquizartinibO-demethylated quizartinib