FI-700

FI-700 is an orally active FLT3 inhibitor with an IC₅₀ of 20 nM. FI-700 induces G1 phase cell cycle arrest by inhibiting autophosphorylation of mutant FLT3 and the downstream STAT5/MAPK pathway. FI-700 triggers the mitochondrial apoptosis pathway by downregulating anti-apoptotic proteins Mcl-1 and Bcl-XL, altering the conformation of Bax, and activating caspase-3. FI-700 can be used in research related to acute myeloid leukemia^[1][2]. In Vitro:FI-700 (0.01-0.1 μM; 72 h) selectively inhibits the growth of mutant FLT3 cells in human leukemia cell lines (MV4;11, MOLM-13, THP1, Kasumi-1, K562)^[1].
FI-700 (0.03-1.0 μM; 6 h) inhibits constitutive phosphorylation of FLT3, STAT5 and MAPK in MOLM-13 cells^[1].
FI-700 (100 nM; 48 h) selectively reduces the growth of primary human AML cells harboring FLT3/ITD or FLT3/D835Y mutations^[1].
FI-700 (0.01-0.3 μM; 24 h) induces G1-phase cell cycle arrest and increases the population of sub-G1 apoptotic cells in MOLM-13 cells^[1].
FI-700 (200-800 nM; 24-72 h) induces apoptosis, reduces Mcl-1 and Bcl-XL expression, induces Bax conformational changes, and activates caspase-3 in MOLM-13 cells^[2].
FI-700 potently inhibits the activity of recombinant human FLT3 kinase with an IC₅₀ of 20 nM, and exhibits relative selectivity against other tyrosine kinases as well as serine/threonine kinases^[1]. In Vivo:FI-700 (100-200 mg/kg; p.o.; twice daily for 5 consecutive days; observation for 10 days) induces tumor regression in a subcutaneous MOLM-13 tumor xenograft mouse model^[1].
FI-700 (200 mg/kg; p.o.; twice daily for 5 consecutive days; survival monitored up to day 60) significantly prolongs the survival of mice in the intravenous MOLM-13 xenograft mouse model^[1].
FI-700 (200 mg/kg; p.o.; twice daily; for 4 consecutive days; sacrificed on day 13) exerts effects of eliminating leukemia cells in peripheral blood and bone marrow without inducing severe myelosuppression in a syngeneic transplanted C3H/Hej mouse model^1].