FLT3-IN-40

FLT3-IN-40 (compound 1) is a type I ATP-competitive FLT3 inhibitor with an IC50 of 16.26 nM. It reduces the autophosphorylation levels of FLT3 and the phosphorylation levels of downstream ERK. FLT3-IN-40 exhibits antiproliferative activity, cell cycle regulation, and apoptosis induction. It is applicable in research related to acute myeloid leukemia.

FLT3-IN-40 (compound 1) is an effective inhibitor of MV4-11 cell proliferation, with an IC50 of 0.0021 nM, demonstrating a progressive biphasic dose-response. As an ATP-competitive type I FLT3 inhibitor, FLT3-IN-40 (0.001-10 nM) inhibits purified FLT3 kinase with an IC50 of 16.26 nM and exhibits an IC50 of 0.80 nM for inhibiting p-ERK signaling in MV4-11 cells. It also suppresses Molm14 cell proliferation, yielding an IC50 of 1.42 nM, and shows significantly less antiproliferative activity against K562 cells (IC50 1583 nM) and Ba/F3 cells (IC50 8467 nM), which lack FLT3 activating mutations. At picomolar concentrations (1 pM-10 nM; 72 h), FLT3-IN-40 induces minimal apoptosis in MV4-11 cells but significantly triggers early (17.3%) and late (10.3%) apoptosis at 10 nM after 72 hours. This compound induces moderate G1 phase arrest stabilization at picomolar concentrations and strong G1 phase cell cycle arrest following 10 nM treatment for 72 hours. Additionally, FLT3-IN-40 exhibits high kinase selectivity, binding strongly only to FLT3 among 96 tested kinases at concentrations of 1 nM and 10 nM.