ODM-203 is a dual inhibitor of VEGFR and FGFR (IC50s = 5-26 and 6-35 nM for VEGFR1-3 and FGFR1-4, respectively).1 It is selective for VEGFR1-3 and FGFR1-4 over a panel of 308 kinases at 1 ?M, but does inhibit the receptor tyrosine kinases PDGFRα, PDGFRβ, and DDR1 (IC50s = 35, 169, and 6 nM, respectively), as well as MAP4K4, MINK1, RET, SIK2, YES1, and Tie2 (IC50s = 49, 41, 8, 23, 152, and 174 nM, respectively). ODM-203 inhibits FGFR-dependent proliferation in H1581 lung, SNU-16 stomach, and RT4 bladder cancer cells (IC50s = 104, 132, and 192 nM, respectively) and VEGF-induced tube formation by human umbilical vein endothelial cells (HUVECs; IC50 = 33 nM). In vivo, ODM-203 (20 and 40 mg/kg) decreases tumor volume in an RT4 mouse xenograft model. It also reduces tumor growth and intratumor phosphorylation of FGFR in a SNU-16 mouse xenograft model when administered at a dose of 30 mg/kg.
1.Holmstr?m, T.H., Moilanen, A.-M., Ikonen, T., et al.ODM-203, a selective inhibitor of FGFR and VEGFR, shows strong antitumor activity, and induces antitumor immunityMol. Cancer Ther.18(1)28-38(2019)