Table 3.

FLT3 inhibitors currently in clinical trials for AML

Compound	Chemical class	Manufacturer	Targeted kinases	FLT3 IC50,* nM	Selected clinical trials
PKC412	Benzoyl-staurosporine	Novartis (Basel, Switzerland)	PKC, PDGFR, KDR, KIT, FLT3, ABL, FGFR1, FGFR3	528	Stone et al67: Phase 2 trial in advanced MDS or relapsed or refractory AML with FLT3-ITD or FLT3-TKD
CEP-701 (lestaurtinib)	Indolocarbazole	Cephalon (Frazer, PA)	FLT3, TRKA, KDR, PKC, PDGFR, EGFR	2-3	Smith et al68; Phase 1/2 trial in refractory, relapsed, or poor-risk AML with FLT3-ITD or FLT3-TKD mutations
MLN518 (CT53518, tandutinib)	Piperazinyl quinazoline	Millennium (San Francisco, CA)	KIT, PDGFR, FLT3, FMS	170-220	De Angelo et al69: Phase 2 trial in relapsed, refractory, or untreated (not fit for induction therapy) AML with FLT3-ITD
SU11248 (sunitinib malate)	Indolinone	Pfizer (New York, NY; synthesized by Sugen, South San Francisco, CA)	FLT3, KDR, PDGFR, KIT, VEGFR	10	O'Farrell et al70: Phase 1 trial in refractory, relapsed, or untreated AML; Fiedler et al71: Phase 1 trial in relapsed or refractory AML with FLT3-ITD or FLT3-TKD

Data from Wadleigh et al,⁷² Chen et al,⁷³ Chen et al,⁷⁴ and Mendel et al.⁷⁵

IC₅₀ indicates the half-maximal inhibitory concentration in vitro; FLT3-ITD, internal tandem duplication of the FLT3 gene; and FLT3-TKD, activating point mutations in codon 835 or 836 of the FLT3 gene.

^*FLT3 autophosphorylation in vitro.