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 |
| 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.