Denfivontinib (G-749) is a potent, broad-spetrum FLT-3 inhibitor with IC50 of 0.4 and 0.6 nM against wt FLT-3 and FLT3-D835Y mutant, respectively.
G-749 also shows potent and sustained inhibition of the FLT3 mutants including FLT3-ITD, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays.
G-749 also inhibits RTKs Ret, FLT1, Axl, Fms, FGFR-1/3 (IC50=9-30 nM), and Aurora A and B (IC50=6-24 nM) inhibits autophosphorylation of FLT3 with IC50 of <8 nM in FLT3-WT bearing RS4-11 and in FLT3-ITD harboring MV4-11 and Molm-14 cells.
G-749 shows potent antileukemic activity in patient blasts harboring FLT3-ITD, FLT3-TKD, and FLT3-ITD/TKD mutations through inhibition of pFLT3 and pERK1/2 both in vitro and in vivo, overcomes drug resistance of AC220 and/or PKC412.
