product name BFH772
Description: BFH772 (also known as BFH-772) is a novel and potent orally bioavailable VEGFR2 inhibitor that targets VEGFR2 kinase with IC50 of 3 nM. 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.
References: J Med Chem. 2016 Jan 14;59(1):132-46.
439.39
Formula
C23H16F3N3O3
CAS No.
890128-81-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 87 mg/mL (198.0 mM)
Water: <1 mg/mL
Ethanol: 87 mg/mL (198.0 mM)
Solubility (In vivo)
Synonyms
BFH 772, BFH-772
other peoduct :
| In Vitro |
In vitro activity: BFH772 was highly effective at targeting VEGFR2 kinase with an IC50 value of 3 nM, however, lost 500-fold potency on FLK-1, FLT-1, and FLT-4. BFH772 was highly selective, In addition to VEGFR2, it also targeted B-RAF, RET, and TIE-2, albeit with at least 40-fold lower potency. BFH772 inhibits the ligand induced autophosphorylation of RET, PDGFR, and KIT kinases, with IC50 values ranging between 30 and 160 nM. Kinase Assay: 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. Cell Assay: Subconfluent HUVECs were incubated in triplicate in 96-well plates with basal medium containing 1.5% FCS and a constant concentration of VEGF (10 ng/mL), bFGF (0.5 ng/mL), or FCS (5%) in the presence or absence of compounds. After 24 h of incubation, BrdUrd labeling solution was added and cells incubated an additional 24 h before fixation, blocking, and addition of peroxidaselabeled anti-BrdUrd antibody. Bound antibody was then detected spectrophotometrically at 450 nm. |
|---|---|
| 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. |
| Animal model | Sprague−Dawley rats |
| Formulation & Dosage | Dissolved in N-methyl pyrrolidone/polyethylene glycol200(30:70, v/v); 1 mg/kg; i.v. injection |
| References | J Med Chem. 2016 Jan 14;59(1):132-46. |
