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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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500mg |
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Purity: ≥98%
NVP-BHG712 (NVP BHG-712; NVP BHG712; BHG-712) is a selective and orally bioavailable EphB4 inhibitor with potential anticancer activity. It has an IC50 of 25 nM for EphB4 and IC50s of 0.40 μM, 1.27 μM, and 1.67 μM for c-Raf, c-Src, and c-Abl, respectively, for other kinases. When profiled against other kinases in biochemical as well as cell-based assays, NVP-BHG712 showed high selectivity for targeting the EphB4 kinase. It inhibits EphB4 kinase activity in the low nanomolar range. Following oral administration, BHG-712 exhibits excellent pharmacokinetic characteristics and effectively inhibits EphB4 autophosphorylation in tissues.
Targets |
EphA2 (IC50 = 3.3 nM); EphB4 (IC50 = 3 nM)
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ln Vitro |
NVP-BHG712 treatment also inhibits RTK autophosphorylation in stable transfected A375 melanoma cells with an EC50 of 25 nM for EphB4 and 4.2 μM for VEGFR2, respectively. [1]
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ln Vivo |
NVP-BHG712 (3 mg/kg, p.o.) significantly reduces VEGF-stimulated tissue formation and vascularization in a model of growth factor-induced angiogenesis by inhibiting EphB4 forward signaling. The potent reversal of VEGF-enhanced tissue formation and vessel growth is another benefit of NVP-BHG712 (10 mg/kg/kg, p.o.). The long-lasting exposure of NVP-BHG712 (3 mg/kg, p.o.) results in a long-lasting inhibition of EphB4 kinase activity in mice, with concentrations of around 10 μM in plasma as well as in lung and liver tissue for up to 8 hours. [1]
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Enzyme Assay |
NVP-BHG712 is a specific EphB4 inhibitor with an ED50 of 25 nM that distinguishes between EphB4 and VEGFR inhibition; it also exhibits activity against c-Raf, c-Src, and c-Abl with IC50 values of 0.395 μM, 1.266 μM and 1.667 μM, respectively.
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Cell Assay |
NVP-BHG712 inhibited the autophosphorylation of different EphRs in Hek293 cells after transfection. EphB4 was more inhibited by NVP-BHG712 than EphB2, EphA2, EphB3, and EphA2.
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Animal Protocol |
VEGF-mediated angiogenesis in vivo is induced in a growth factor implant model in mice.
≤30 mg/kg Administered via p.o. |
References |
Molecular Formula |
C26H20F3N7O
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Molecular Weight |
503.48
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Exact Mass |
503.489
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Elemental Analysis |
C, 62.02; H, 4.00; F, 11.32; N, 19.47; O, 3.18
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CAS # |
940310-85-0
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Related CAS # |
NVP-BHG712 isomer;2245892-85-5
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Appearance |
Solid powder
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SMILES |
CC1=C(C=C(C=C1)C(=O)NC2=CC=CC(=C2)C(F)(F)F)NC3=C4C=NN(C4=NC(=N3)C5=CN=CC=C5)C
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InChi Key |
ZCCPLJOKGAACRT-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C26H20F3N7O/c1-15-8-9-16(25(37)32-19-7-3-6-18(12-19)26(27,28)29)11-21(15)33-23-20-14-31-36(2)24(20)35-22(34-23)17-5-4-10-30-13-17/h3-14H,1-2H3,(H,32,37)(H,33,34,35)
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Chemical Name |
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: NMP+polyethylene glycol 300 (10/90, v/v): 30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9862 mL | 9.9309 mL | 19.8618 mL | |
5 mM | 0.3972 mL | 1.9862 mL | 3.9724 mL | |
10 mM | 0.1986 mL | 0.9931 mL | 1.9862 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NVP-BHG712 inhibits multiple Eph receptor kinases in cell based assays.Angiogenesis.2010 Sep;13(3):259-67. td> |
NVP-BHG712 inhibits endogenous EphB4 autophosphorylation in lung tissue of mice and has micromolar exposure in plasma and tissues.Angiogenesis.2010 Sep;13(3):259-67. td> |
Soluble EphB4-Fc protein inhibits VEGF driven tissue growth and angiogenesis.Angiogenesis.2010 Sep;13(3):259-67. td> |