Motesanib Diphosphate (AMG-706)
For research use only.
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.
Selleck's Motesanib Diphosphate (AMG-706) has been cited by 6 publications
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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.
(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.
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 to the product individually and in order(Data is from Selleck tests instead of citations):
For best results, use promptly after mixing.
* 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.
In vivo Formulation Calculator (Clear solution)
|Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)|
|Dosage||mg/kg||Average weight of animals||g||Dosing volume per animal||ul||Number of animals|
|Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)|
|% DMSO % % Tween 80 % ddH2O|
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
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Molecular Weight Calculator
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01386866||Completed||Drug: AMG 706||Advanced Solid Tumors||Amgen||May 2009||Phase 1|
|NCT00448786||Completed||Drug: AMG 706||Solid Tumors||Amgen||February 2007||Phase 1|
|NCT00322400||Completed||Drug: Docetaxel|Drug: Paclitaxel|Drug: AMG 706||Locally Recurrent and Metastatic Breast Cancer||Amgen||March 2006||Phase 1|
|NCT01235416||Completed||Drug: AMG 706||Histologically or Cytologically Documented Solid Tumors||Amgen||September 2005||Phase 1|
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.
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