Motesanib Diphosphate (AMG-706)
Molecular Weight(MW): 569.44
Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; similar activity against Kit, ~10-fold more selective for VEGFR than PDGFR and Ret. Phase 3.
3 Customer Reviews
(C, D, E)VEGFCM stimulated CXCR4 expression in CSC 24 h after VEGFCM treatment. CSC were untreated (Control, C), or treated with VEGFMSC-conditioned medium (VEGFCM, D) or VEGFCM and VEGFR1 inhibitor AMG(E) followed by flow cytometry. AMG inhibited the expression of VEGFCM-induced CXCR4. (F) Quantitative analysis of CXCR4 expression by flow cytometry. CSC were treated with CtrlCM or VEGFCM with or without VEGFR specific inhibitors for VEGFR1 (AMG), VEGFR2 (VEGFR2-I), and VEGFR3 (MAZ).*P , 0.05 vs. control, AMG, VEGFR2-I. and MAZ; #P , 0.05 vs. AMG and MAZ (n = 5). (G) CtrlCM promoted CSC migration. *P , 0.05 vs. CtrlCM; OP , 0.01 vs. CtrlCM; &P , 0.05 vs. CtrlCM+AMG and <sup>Ctrl</sup>CM+MAZ (n ?15); @P , 0.01 vs. CtrlCM; PP , 0.01 vs. CtrlCM; $P , 0.05 vs. CtrlCM+AMG and CtrlCM+MAZ. Note: CtrlCM= CtrlMSC< mesenchymal stem cells>-conditioned medium
Cardiovasc Res 2011 91, 402-11. Motesanib Diphosphate (AMG-706) purchased from Selleck.(F ) Quantitative analysis of CXCR4 expression by flow cytometry. CSC were treated with CtrlCM or VEGFCM with or without VEGFR specific inhibitors for VEGFR1 (AMG), VEGFR2 (VEGFR2-I), and VEGFR3 (MAZ). *P<0.05 vs. control, AMG, VEGFR2-I. and MAZ; #P<0.05 vs. AMG and MAZ ( n=5). ( G ) VEGFCM promoted CSC migration. *P<0.05 vs. CtrlCM; ▲P<0.01 vs. CtrlCM; &P<0.05 vs. CtrlCM+ AMG and CtrlCM+ MAZ ( n=15); @P <0.01 vs. CtrlCM; P <0.01 vs. CtrlCM; $P <0.05 vs. VEGFCM+ AMG and VEGFCM+ MAZ.
Cardiovasc Res 2011 91, 402-11. Motesanib Diphosphate (AMG-706) purchased from Selleck.
Immunofluorescence staining of choroidal neovascularization (CNV) lesions 14 days after laser photocoagulation. Choroidal flat mounts were fluorescently labeled with F-actin-specific marker phalloidin (green channel), endothelial cell marker CD34 (red channel), and nuclear marker DAPI (blue channel). CNV lesions in topical vehicle-treated eye (A, C, E and G) and topical motesanib-treated eye (B, D, F and H). The scale bar represents 100 um.
J Ocul Pharmacol Ther 2014 10.1089/jop.2014.0023. Motesanib Diphosphate (AMG-706) purchased from Selleck.
Purity & Quality Control
Choose Selective VEGFR Inhibitors
|Description||Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; similar activity against Kit, ~10-fold more selective for VEGFR than PDGFR and Ret. Phase 3.|
Motesanib Diphosphate has broad activity against the human VEGFR family, and displays >1000 selectivity against EGFR, Src, and p38 kinase. Motesanib Diphosphate significantly inhibits VEGF-induced cellular proliferation of HUVECs with an IC50 of 10 nM, while displaying little effect at bFGF-induced proliferation with an IC50 of >3,000 nM. Motesanib Diphosphate also potently inhibits PDGF-induced proliferation and SCF-induced c-kit phosphorylation with IC50 of 207 nM and 37 nM, respectively, but not effective against the EGF-induced EGFR phosphorylation and cell viability of A431 cells.  Althouth displaying little antiproliferative activity on cell growth of HUVECs alone, Motesanib Diphosphate treatment significantly sensitizes the cells to fractionated radiation. 
|In vivo||Administration of Motesanib Diphosphate at 100 mg/kg significantly inhibits VEGF-induced vascular permeability in a time-dependent manner. Oral administration of Motesanib Diphosphate twice daily or once daily potently inhibits, in a dose-dependent manner, VEGF-induced angiogenesis using the rat corneal model with ED50 of 2.1 mg/kg and 4.9 mg/kg, respectively. Motesanib Diphosphate induces a dose-dependent tumor regression of established A431 xenografts by selectively targeting neovascularization in tumor cells.  Administration of Motesanib Diphosphate in combination with radiation displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models.  Motesanib Diphosphate treatment also induces significant dose-dependent reductions in tumor growth and blood vessel density of MCF-7, MDA-MB-231, or Cal-51 xenografts, which can be markedly enhanced when combined with docetaxel or tamoxifen. |
In vitro kinase assays:Optimal enzyme, ATP, and substrate (gastrin peptide) concentrations are established for each enzyme using homogeneous time-resolved fluorescence (HTRF) assays. Motesanib Diphosphate is tested in a 10-point dose-response curve for each enzyme using an ATP concentration of two-thirds Km for each. Most assays consist of enzyme mixed with kinase reaction buffer [20 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 5 mM MnCl2, 100 mM NaCl, 1.5 mM EGTA]. A final concentration of 1 mM DTT, 0.2 mM NaVO4, and 20 μg/mL BSA is added before each assay. For all assays, 5.75 mg/mL streptavidin-allophycocyanin and 0.1125 nM Eu-PT66 are added immediately before the HTRF reaction. Plates are incubated for 30 minutes at room temperature and read on a Discovery instrument. IC50 values are calculated using the Levenberg-Marquardt algorithm into a four-parameter logistic equation.
|In vitro||DMSO||100 mg/mL warmed (175.61 mM)|
|Water||19 mg/mL warmed (33.36 mM)|
|In vivo||Add solvents individually and in order:
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01386866||Completed||Advanced Solid Tumors||Amgen||May 2009||Phase 1|
|NCT00427349||Completed||Gastrointestinal Carcinoid Tumor|Islet Cell Tumor|Neoplastic Syndrome||Eastern Cooperative Oncology Group|National Cancer Institute (NCI)||September 2008||Phase 2|
|NCT00574951||Completed||Fallopian Tube Cancer|Ovarian Cancer|Primary Peritoneal Cavity Cancer||Gynecologic Oncology Group|National Cancer Institute (NCI)||December 2007||Phase 2|
|NCT00460317||Terminated||Non-Small Cell Lung Cancer||Amgen|Takeda||July 2007||Phase 3|
|NCT00448786||Completed||Solid Tumors||Amgen||February 2007||Phase 1|
|NCT00369070||Terminated||Advanced Non-squamous NSCLC||Amgen||January 2007||Phase 2|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.