NVP-BHG712

Names

[ Name ]:
NVP-BHG712

[Synonym ]:
NVP-BHG712
4-Methyl-3-{[1-methyl-6-(3-pyridinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino}-N-[3-(trifluoromethyl)phenyl]benzamide
4-Methyl-3-[[1-methyl-6-(3-pyridinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino]-N-[3-(trifluoromethyl)phenyl]benzamide
cc-540
S2202_Selleck

Biological Activity

[Description]:

NVP-BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM that discriminates between VEGFR and EphB4 inhibition; also shows activity against c-Raf, c-Src and c-Abl with IC50 of 0.395 μM, 1.266 μM and 1.667 μM, respectively.IC50 value: 25 nM(EC50)Target: EphB4 receptor;c-Raf; c-Srcin vitro: NVP-BHG712 treatment also dose dependently leads to the inhibition of RTK autophosphorylation in stable transfected A375 melanoma cells with EC50 of 25 nM and 4.2 μM for EphB4 and VEGFR2, respectively [1].in vivo: In a growth factor-induced angiogenesis model, NVP-BHG712 (3 mg/kg, p.o) significantly suppresses VEGF stimulated tissue formation and vascularization by inhibiting EphB4 forward signaling. Furthermore, NVP-BHG712 (10 mg/kg/kg, p.o.) potently reverses VEGF enhanced tissue formation and vessel growth. NVP-BHG712 (3 mg/kg, p.o.) shows a long lasting exposure with concentrations around 10 μM in plasma as well as in lung and liver tissue for up to 8 hours, and thus results in a long lasting inhibition of EphB4 kinase activity in mice [1].

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Ephrin Receptor

Research Areas >> Cancer

[References]

[1]. Martiny-Baron G, et al. The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis. Angiogenesis. 2010 Sep;13(3):259-67.

[Related Small Molecules]

ALW-II-41-27 | XL-647 | JI-101

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Molecular Formula ]:
C₂₆H₂₀F₃N₇O

[ Molecular Weight ]:
503.478

[ Exact Mass ]:
503.168152

[ PSA ]:
101.11000

[ LogP ]:
4.05

[ Appearance of Characters ]:
white to beige

[ Index of Refraction ]:
1.666

[ Storage condition ]:
?20°C

[ Water Solubility ]:
DMSO: >15mg/mL

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310

[ Hazard Codes ]:
T

[ Risk Phrases ]:
25

[ Safety Phrases ]:
45

[ RIDADR ]:
UN 2811 6.1 / PGIII

Articles

EphB4 forward signalling regulates lymphatic valve development.

Nat. Commun. 6 , 6625, (2015)

Bidirectional signalling is regarded as a notable hallmark of the Eph-ephrin signalling system: Eph-dependent forward signalling in Eph-expressing cells and ephrin-dependent reverse signalling in Ephr...

EPHB4 Protein Expression in Vascular Smooth Muscle Cells Regulates Their Contractility, and EPHB4 Deletion Leads to Hypotension in Mice.

J. Biol. Chem. 290 , 14235-44, (2015)

EPH kinases are the largest family of receptor tyrosine kinases, and their ligands, ephrins (EFNs), are also cell surface molecules. This work presents evidence that EPHB4 on vascular smooth muscle ce...

Effect of EPH-ephrin signaling on the growth of human leukemia cells.

Anticancer Res. 34(6) , 2913-8, (2014)

Signaling induced by binding of erythropoietin-producing hepatoma-amplified sequence (EPH) receptors to their cell-surface ephrin ligands is implicated in hematopoiesis and growth of various cancer ce...