Quizartinib hydrochloride

Quizartinib dihydrochloride (AC220 dihydrochloride) is the dihydrochloride salt form of Quizartinib (HY-13001). Quizartinib dihydrochloride is an orally active, highly selective and potent second-generation type II FLT3 tyrosine kinase inhibitor, with a Kd of 1.6 nM. Quizartinib dihydrochloride inhibits wild-type FLT3 and FLT3-ITD autophosphorylation in MV4-11 cells with IC50s of 4.2 and 1.1 nM, respectively. Quizartinib dihydrochloride can be linked to the VHL ligand via an optimized linker to form a PROTAC FLT3 degrader. Quizartinib dihydrochloride induces apoptosis[1][2][3].

As a second-generation FLT3 inhibitor, Quizartinib demonstrates more advantages than first-generation FLT3 inhibitors in terms of tolerability, efficacy and oral pharmacokinetic properties.

Synthesis route of Quizartinib hydrochloride

[1] Zarrinkar PP, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood, 2009, 114(14), 2984-2992. DOI:10.1182/blood-2009-05-222034
[2] Puissant A, et al. SYK is a critical regulator of FLT3 in acute myeloid leukemia. Cancer Cell. 2014 Feb 10;25(2):226-42. DOI:10.1016/j.ccr.2014.01.022
[3] Sun X, et al. PROTACs: great opportunities for academia and industry. Signal Transduct Target Ther. 2019 Dec 24;4:64. DOI:10.1038/s41392-019-0101-6