Summary of preclinical characteristics of FLT3-TKI used in clinical trials
| TKI . | Structural class . | Additional targets . | IC50 FLT3 tyrosine phosphorylation, nM . | IC50 cell growth, nM . | Prolongation of survival in murine models of FLT3-ITD–induced disease . | Reference . |
|---|---|---|---|---|---|---|
| Midostaurin (PKC412) | Indolocarbazole alkaloide | c-FMS, c-KIT, PDGFRα/β | 10 | < 30 | + | 89 |
| Lestaurtinib (CEP-701) | Indolocarbozole alkaloide | TrkA, VEGFR | 2-5 | 2-3 | + | 50, 123 |
| Sorafinib (BAY 43-9006) | Biaryl urea derivate | c-RAF, VEGFR, PDGFR, c-KIT | 2.8 | 0.88 | + | 54, 124, 125 |
| Semaxanib (SU5416) | Indolinone derivate | VEGFR, c-KIT | 100 | 250 | Not reported | 126, 127 |
| Sunitinib (SU11248) | Indolinone derivate | VEFGR, PDGFR, c-KIT | 50 | 8 | + | 128, 129 |
| Tandutinib (MLN-518) | Piperazinyl quinazoline | c-KIT, PDGFR | 30-100 | 10-30 | + | 130,–132 |
| KW-2449 | Not disclosed yet | ABL, FGFR1, Aurora kinase | 13.1 | 11-24 | + | 133 |
| AC220 | Bis-aryl urea derivate | c-KIT, RET, PDGFR, CSF1R | 1.1 | 0.56 | + | 66 |
| TKI . | Structural class . | Additional targets . | IC50 FLT3 tyrosine phosphorylation, nM . | IC50 cell growth, nM . | Prolongation of survival in murine models of FLT3-ITD–induced disease . | Reference . |
|---|---|---|---|---|---|---|
| Midostaurin (PKC412) | Indolocarbazole alkaloide | c-FMS, c-KIT, PDGFRα/β | 10 | < 30 | + | 89 |
| Lestaurtinib (CEP-701) | Indolocarbozole alkaloide | TrkA, VEGFR | 2-5 | 2-3 | + | 50, 123 |
| Sorafinib (BAY 43-9006) | Biaryl urea derivate | c-RAF, VEGFR, PDGFR, c-KIT | 2.8 | 0.88 | + | 54, 124, 125 |
| Semaxanib (SU5416) | Indolinone derivate | VEGFR, c-KIT | 100 | 250 | Not reported | 126, 127 |
| Sunitinib (SU11248) | Indolinone derivate | VEFGR, PDGFR, c-KIT | 50 | 8 | + | 128, 129 |
| Tandutinib (MLN-518) | Piperazinyl quinazoline | c-KIT, PDGFR | 30-100 | 10-30 | + | 130,–132 |
| KW-2449 | Not disclosed yet | ABL, FGFR1, Aurora kinase | 13.1 | 11-24 | + | 133 |
| AC220 | Bis-aryl urea derivate | c-KIT, RET, PDGFR, CSF1R | 1.1 | 0.56 | + | 66 |
In addition, several other FLT3-TKI including ABT-869, dovitinib (CHIR-258), and AP24534 have been demonstrated to exhibit pronounced in vitro and in vivo inhibitory activity but have not entered clinical trials yet or results have not been reported so far (reviewed in Weisberg et al).134
PDGFR indicates platelet derived growth factor receptor; VEGFR, vascular endothelial growth factor receptor; and FGFR, fibroblast growth factor receptor.