Ongoing clinical evaluation of anti-FGFR drugs with IC50< 100 nmol against at least one FGFR
| Targets and IC50, nmol/L (if available) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Compound | FGFR1 | FGFR2 | FGFR3 | FGFR4 | VEGFR1 | VEGFR2 | VEGFR3 | PDGFR-α | PDGFR-β | Others [IC50, nmol/L] | Clinical development | Company |
| MultitargetedTKIs | ||||||||||||
| TKI258 (dovitinib; ref. 64) | 8 | 9 | 10 | 13 | 8 | 200 | 27 | FLT-3 [1] | Phase III (RCC) | Novartis | ||
| KIT [2] | ||||||||||||
| CSF-1 [36] | ||||||||||||
| BIBF1120 (nintedanib; ref. 65) | 69 | 37 | 108 | 610 | 34 | 21 | 13 | 59 | 65 | LCK [16] | Phase III (NSCLC, ovarian) | Boehringer-Ingelheim |
| FLT-3 [26] | ||||||||||||
| SRC [156] | ||||||||||||
| LYN [195] | ||||||||||||
| E3810 (66) | 17.5 | 82.5 | 237.5 | >1,000 | 7 | 25 | 10 | 175 | 525 | CSF-1 [5] | Phase 1 (solid tumors) | Ethical Oncology of Science |
| KIT [456] | ||||||||||||
| E7080 (lenvat-inib; ref. 67) | 46 | 22 | 4 | 5.2 | 51 | 39 | KIT [100] | Phase III (thyroid) | Eisai | |||
| BMS582664 (brivanib; ref. 68) | 148 | 125 | 68 | 380 | 25 | 10 | >6,000 | Phase III (HCC, CRC) | Bristol-Myers Squibb | |||
| ENMD-2076 (69) | 93 | 71 | 500 | 58 | 16 | 56.4 | FLT-3 [2] | Phase II (breast, ovarian) | Entremed | |||
| RET [10.4] | ||||||||||||
| SRC [20.2] | ||||||||||||
| CSF-1 [24.8] | ||||||||||||
| Aurora A [14] | ||||||||||||
| Aurora B [350] | ||||||||||||
| KIT [120] | ||||||||||||
| TSU68 (orantinib; ref. 70) | 1.2μmol/L | 2.1 μmol/L | 0.008 μmol/L | Phase III (HCC) | Taiho Pharmaceutical | |||||||
| AP24534 (ponatinib; ref. 71) | 2 | 2 | 18 | 8 | 1.5 | 1.1 | ABL [0.7] | Phase II (ALL, CML) | Ariad | |||
| SRC [5.4] | ||||||||||||
| LYN [0.24] | ||||||||||||
| KIT [12.5] | ||||||||||||
| Selective TKIs | ||||||||||||
| AZD4547 (72) | 0.2 | 2.5 | 1.8 | 165 | 24 | IGFR [581] | Phase II (breast, gastric) | AstraZeneca | ||||
| BGJ398 (73) | 0.9 | 1.4 | 1 | 60 | Phase 1 (solid tumors) | Novartis | ||||||
| LY2874455 (74) | 2.8 | 2.6 | 6.4 | 6 | 7a | Phase 1 (solid tumors) | Eli Lilly | |||||
| Monoclonal antibodies | ||||||||||||
| MGFR1877S [cl in icalt rials.gov] | Phase I (MM, solid tumors) | Genentech | ||||||||||
| FGF traps | ||||||||||||
| HGS1036/FP-1039(75) | FGF1 | Phase I (solid tumors) | Human Genomic Sciences | |||||||||
| FGF2 | ||||||||||||
| FGF4 | ||||||||||||
aSix- to 9-fold cellular and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice.
Abbreviations: ALL, acute lymphoblastic leukemia: CML, chronic myeloid leukemia: CRC, colorectal cancer: FLT-3, Fms-like tyrosine kinase receptor 3: HCC, hepatocellular carcinoma: IGFR, insulin-like growth factor receptor: MM, multiple myeloma: RCC, renal cell carcinoma: STS, soft tissue sarcoma.