Table 1.
Agent | IC50, nM | Other targets | Clinical phase | ||
---|---|---|---|---|---|
VEGFR-1, -2, -3 | PDGFR-α, -β | FGFR-1, -2, -3 | |||
Sorafenib [77] | NR, 90, 20a | NR, 57a | 580, NR, NR | c-kit, FLT-3, Raf | III |
Sunitinib [78] | NR, 80, NR | NR, 2 | 2,900, NR, NR | c-kit, FLT-3, CSF-1R, RET | III |
Cediranib [79] | 5, 1, 3 | 36, 5 | 26, NR, NR | c-kit | III |
Motesanib [80] | 2, 3, 6 | NR, 84 | >2,800, NR, NR | c-kit, RET | III |
Axitinib [81] | NRb | NRb | NR | c-kit | II |
Linifanib [82] | 3, 4, 190 | NR, 66 | >12,500, NR, NR | FLT-3, CSF-1R, c-kit | II |
Brivanib [83,84]c | 380, 25, 10 | NR, >6,000 | 148, 125, 68 | NR | II |
BIBF 1120 [85] | 34, 21, 13 | 59, 65 | 69, 37, 108 | FLT-3, src | III |
Pazopanib [86] | 10, 30, 47 | 71, 84 | 140, NR, 130 | c-kit | II/III |
IC50 values of sorafenib against murine VEGFR-3 and PDGFR-β.
Axitinib reportedly inhibits VEGFRs at subnanomolar concentrations and PDGFR-β at low-nanomolar concentrations [81].
IC50 values for brivanib (BMS-582664) are reported for BMS-540215, the active moiety hydrolyzed in vivo.
c-kit, stem cell factor receptor; CSF-1R, colony stimulating factor 1 receptor; FGFR, fibroblast growth factor receptor; FLT-3, fms-like tyrosine kinase 3; IC50, half maximal inhibitory concentration; NR, not reported; PDGFR, platelet-derived growth factor receptor; Raf, v-raf 1 murine leukemia viral oncogene homolog 1; RET, rearranged during transfection; VEGFR, vascular endothelial growth factor receptor.