| References: |
BFH772 is a potent oral VEGFR2 inhibitor, which is highly effective at targeting VEGFR2 kinase with an IC50 value of 3 nM.InVitro: BFH772 is highly selective; apart from inhibiting VEGFR2 at 3 nM IC50, it also targets B-RAF, RET, and TIE-2, albeit with at least 40-fold lower potency. BFH772 is inactive (IC50>10 μM; >2 μM for cKIT) against all other tyrosine specific- and serine/threonine-specific protein kinases tested. BFH772 inhibits VEGFR2 with IC50 of 4.6±0.6 nM in CHO cells. BFH772 inhibits VEGFR2 with IC50 of 3 nM in HUVEC cells. BFH772 inhibits the ligand induced autophosphorylation of RET, PDGFR, and KIT kinases, with IC50 values ranging between 30 and 160 nM. BFH772 is selective (IC50 values >0.5 μM) against the kinases of EGFR, ERBB2, INS-R, and IGF-1R and against the cytoplasmic BCR-ABL kinase. IC50 of BFH772 (<0.01 nM, n=2) demonstrates that they abrogated VEGF induced proliferation at remarkably low nM concentrations.
InVivo: BFH772 at 3 mg/kg orally dosed once per day potently inhibits melanoma growth (by 54-90% for primary tumor and 71-96% for metastasis growth) as depicted by treatment to control ratios. Dose–response curves of BFH772 at 0.3, 1, and 3 mg/kg demonstrate that even at the lowest concentrations, this naphthalene-1-carboxamide inhibits VEGF induced tissue weight and TIE-2 levels but only reaches statistical significance at 1 mg/kg and above. |
