Table 1.
Characteristics of FLT3 inhibitors.
| Class | FLT3 inhibitor | Type | FLT3-TKD inhibition | Non-FLT3 targets | Major toxicities | Approval status |
|---|---|---|---|---|---|---|
| First generation | Lestaurtinib | Type I | Yes | JAK 2/3, TrKA | Infection | Investigated for FLT3 mutated AML, pancreatic cancer, and prostate cancer |
| Midostaurin | Type I | Yes | c-KIT, PKC, PDGFR-α/β, VEGFR-2, SRC | GI toxicity, myelosuppression, pulmonary toxicity | US FDA and EMA approved for adults with newly diagnosed FLT3 mutated AML in combination with intensive chemotherapy and mast cell leukemia | |
| Sorafenib | Type II | No | c-KIT, PDGFR-β, RAF-1, BRAF, mBRAF, VEGFR (1,2,3), RET, RET/PTC | Rash, myelosuppression, QTcF prolongation, elevated liver transaminases | Available off-label (US FDA approved for RCC, differentiated thyroid cancer, and hepatocellular) |
|
| Sunitinib | Type I | Yes | c-KIT, PDGFR-α/β, VEGFR (1,2,3), RET, CSF-1R | GI toxicity, rash, headache | Available off-label (US FDA approved for GIST, pancreatic neuroendocrine tumors, and RCC) |
|
| Second generation | Crenolanib | Type I | Yes | PDGFR-α/β, ULK2, SNARK, CDK7, MLK1, JAK3, TrKA, TYK2, ROCK2 | GI toxicity, elevated liver transaminases | Investigated for FLT3 mutated AML and GIST |
| Gilteritnib | Type I | Yes | AXL, LTK, ALK | GI toxicity, elevated liver transaminases | US FDA approved for adult with relapsed and refractory FLT3 mutated AML | |
| Ponatinib | Type II | No | c-KIT, PDGFR-α, VEGFR-2, FGFR-1, RET, BCR/ABL, SRC, TIE2, EPHR | Hypertension, pancreatitis, arterial thrombosis | US FDA approved for CML, GIST, Ph+ ALL | |
| Quizartinib | Type II | No | c-KIT, PDGFR-β, RET | QTcF prolongation, myelosuppression | Approved in Japan FDA did not grant approval for relapsed and refractory FLT3-ITD mutated AML |
AML, acute myeloid leukemia; CML, chronic myeloid leukemia; CSF-1R, colony stimulating factor receptor Type 1; EMA, European Medicines Agency; EPHR, ephrin receptor; FGFR, fibroblast growth factor receptor; FLT3, FMS-like tyrosine kinase 3; GI, gastrointestinal; GIST, gastrointestinal stromal tumor; ITD, internal tandem duplication; MLK1, mixed-lineage kinase 1; PDGFR, platelet-derived growth factor receptor; PKC, protein kinase C; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia; RCC, renal cell carcinoma; RET, rearranged during transfection; TKD, tyrosine kinase domain; TrKA, Trk system potassium uptake protein; ULK2, Unc-51–like kinase 2; US FDA, United States Food and Drug Administration; VEGFR, vascular endothelial growth factor receptor.