JI6 (JAK3 Inhibitor VI) is a potent, selective and orally active FLT3 inhibitor. JI6 exhibits IC50s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. JI6 also inhibits c-Kit and JAK3, with IC50s of ∼500 and ∼250 nM, respectively. JI6 has research value in acute myeloid leukemia.

JI6 (3-1000 nM; 1-4 days) inhibits MV4-11 cell viability in a dose-dependent manner with IC50 of ∼25 nM. JI6 (1-2000 nM; 48 h) potently inhibits the viability of HCD-57 cells expressing FLT3-ITD, FLT3-D835Y and FLT3-D835H with IC50 of ∼40 nM. JI6 has no effect on the parent HCD-57 or JAK2V617F expressing cells. JI6 (100-500 nM; 24 h) induce apoptosis and cell cycle arrest in HCD-57 cells expressing FLT3-ITD and FLT3-D835Y. JI6 (50-500 nM; 3 h) inhibits phosphorylation of FLT3, ERK and Akt in HCD-57 cells expressing FLT3-ITD and FLT3-D835Y[1].

JI6 (15 mg/kg; i.p. daily for 3 weeks) inhibits the proliferation of HCD-57 expressing FLT3-D835Y in SCID mouse and prolong the survival. JI6 (25 mg/kg; p.o. daily for 3 weeks) inhibits myeloproliferative phenotype in FLT3-ITD knock-in mice. JI6 (100 mg/kg; a single i.p.) significantly inhibits FLT3 phosphorylation and downstream signal transduction in mice expressing FLT3-D835Y[1].