IC50: 3 nM

BFH772 is a VEGFR2 inhibitor.

The VEGF family including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PlGF signals through VEGFR1, VEGFR2, and VEGFR3 cell surface tyrosine kinase receptors that are located on the host vascular endothelium, lymphatic, and hematopoietic systems.

In vitro: BFH772 was highly effective at targeting VEGFR2 kinase, however, lost 500-fold potency on FLK-1, FLT-1, and FLT-4. BFH772 also targeted B-RAF, RET, and TIE-2, albeit with at least 40-fold lower potency. BFH772 inhibited the ligand induced autophosphorylation of RET, PDGFR, and KIT kinases. BFH772 was selective against the kinases of EGFR, ERBB2, INS-R, and IGF-1R and against the cytoplasmic BCR-ABL kinase [1].

In vivo: The dose response curves of BFH772 at 0.3, 1, and 3 mg/kg showed that even at the lowest concentrations, this naphthalene-1-carboxamide inhibited VEGF induced tissue weight and TIE-2 levels but only reached statistical significance at 1 mg/kg and above. Moreover, BFH772 at 3 mg/kg orally dosed once per day could potently inhibit melanoma growth (54-90% for primary tumor and 71-96% for metastasis tumor) when compared with control ratios [1].

Clinical trial: A proof of concept study to evaluate the safety, tolerability, and efficacy of 12 week administration of BFH772 ointment in rosacea patients has completed, but no result data are released [2].

References:[1] Bold G, et al. A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis. J Med Chem. 2016 Jan 14;59(1):132-46.[2] http://adisinsight.springer.com/trials/700244037