Gilteritinib, also known as ASP2215, is a potent FLT3/AXL inhibitor, which showed potent antileukemic activity against AML with either or both FLT3-ITD and FLT3-D835 mutations. In invitro, among the 78 tyrosine kinases tested, ASP2215 inhibited FLT3, LTK, ALK, and AXL kinases by over 50% at 1 nM with an IC50 value of 0.29 nM for FLT3, approximately 800-fold more potent than for c-KIT, the inhibition of which is linked to a potential risk of myelosuppression. ASP2215 inhibited the growth of MV4-11 cells, which harbor FLT3-ITD, with an IC50 value of 0.92 nM, accompanied with inhibition of pFLT3, pAKT, pSTAT5, pERK, and pS6. ASP2215 decreased tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells. ASP2215 may have potential use in treating AML.
Yue, Qinglei; Zhou, Zhiguo; Gao, Qiang; Zheng, Baofu. Preparation of Gilteritinib derivatives as inhibitors of FLT3-Axl. Assignee Shanghai Haoyuan Medchemexpress Co., Ltd., Peop. Rep. China. CN 106083821. (2016).
Shimada, Itsuro; Kurosawa, Kazuo; Matsuya, Takahiro; Iikubo, Kazuhiko; Kondoh, Yutaka; Kamikawa, Akio; Tomiyama, Hiroshi; Iwai, Yoshinori. Preparation of diamino heterocycle-carboxamide compounds as EML4-ALK fusion protein kinase inhibitors. Assignee Astellas Pharma Inc., Japan. WO 2010128659. (2011).
