BFH772 Property

Boiling point:

541.2±50.0 °C(Predicted)

Density 

1.432±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

Soluble in DMSO

form 

A crystalline solid

pka

12.65±0.70(Predicted)

color 

White to off-white

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

BFH772 Chemical Properties,Usage,Production

Description

BFH772 is an inhibitor of VEGF receptor 2 (VEGFR2; IC₅₀ = 0.0027 μM for the human receptor). It is selective for human VEGFR2 over mouse VEGFR2 and human VEGFR1 and VEGFR3 (IC₅₀s = 1.5, 1.7, and 1.1 μM, respectively), as well as 40-fold selective over B-RAF, RET, and Tie2. BFH772 inhibits VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs; IC₅₀ = <0.01 nM). It inhibits VEGF-induced increases in tissue weight and Tie2 levels in an angiogenesis chamber implant model in mice when administered at doses of 1 and 3 mg/kg per day. BFH772 (3 mg/kg per day) inhibits primary tumor and metastasis growth in a B16 melanoma mouse model.

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].

IC 50

3 nm

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