JNJ-38158471

JNJ-38158471 is an inhibitor of VEGFR2 (IC₅₀ = 42 nM).¹ It is selective for VEGFR2 over the PDGFR family kinases CSF-1 receptor tyrosine kinase (FMS), PDGFRα, FMS-related tyrosine kinase 3 (FLT3), and KIT (IC₅₀s = 624, 1,109, 4,810, and 511 nM, respectively) and VEGFR family kinases VEGFR1 and VEGFR3 (IC₅₀s = 4,451 and 1,112 nM, respectively) but does inhibit RET (IC₅₀ = 183 nM). JNJ-38158471 (10, 100, or 500 nM) decreases VEGF-induced phosphorylation of VEGFR2 in serum-starved human umbilical vein endothelial cells (HUVECs). It inhibits VEGF-induced migration in HUVECs when used at a concentration of 1 µM. JNJ-38158471 (100 mg/kg) reduces Vegf-induced corneal neovascularization in mice. It decreases tumor size in an HCT116 colorectal cancer mouse xenograft model when administered at doses ranging from 10 to 200 mg/kg per day. JNJ-38158471 (100 mg/kg per day) reduces polyp number in an Apc^+/Min-FCCC mouse model of spontaneous colorectal adenoma.

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1. LaMontagne, K.R., Butler, J., Borowski, V.B., et al. A highly selective, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor has potent activity in vitro and in vivo. Angiogenesis 12(3), 287-296 (2009).