BFH-772

A potent, selective and orally active VEGFR2 tyrosine kinase inhibitor with IC50 of 3 nM; shows 40-fold less potent activity B-RAF, RET and TIE-2, and >500-fold for FLK-1, FLT-1 and FLT-4; inhibits ligand-induced autophosphorylation of RET, PDGFR and KIT with IC50 of 30-160 nM, potently inhibits VEGF-driven angiogenesis in a chamber model and rodent tumor models at daily doses of less than 3 mg/kg.Psoriasis Phase 2 Discontinued (In Vitro) :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. (In Vivo) :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.

890128-81-1

BFH772 | BFH 772

>98% (HPLC)

DMSO: 7.75 mg/mL

O=C (C1=C2C=CC (OC3=NC=NC (CO) =C3) =CC2=CC=C1) NC4=CC=CC (C (F) (F) F) =C4

C23H16F3N3O3

439.3867

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.