Motesanib-AMG-706-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMotesanibCat. No.: HY-10228CAS No.: 453562-69-1Synonyms: AMG 706;分式: CHNO分量: 373.45作靶点: c-Kit; VEGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 30 mg/mL

2、(80.33 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6777 mL 13.3887 mL 26.7773 mL5 mM 0.5355 mL 2.6777 mL 5.3555 mL10 mM 0.2678 mL 1.3389 mL 2.6777 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Motesanib种有效的 VEGFR1/2/3 的 ATP 竞

3、争性抑制剂，IC50 值为 2 nM/3 nM/6 nM，与对Kit的选择性相似，是PDGFR 和 Ret的 10 倍多。IC50 & Target VEGFR1 VEGFR2 VEGFR32 nM (IC50) 3 nM (IC50) 6 nM (IC50)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 Motesanib has broad activity against the human VEGFR family, and displays 1000 selectivity againstEGFR, Src, and p38

4、 kinase. Motesanib significantly inhibits VEGF-induced cellular proliferation of HUVECswith an IC50 of 10 nM, while displaying little effect at bFGF-induced proliferation with an IC50 of 3,000 nM.Motesanib also potently inhibits PDGF-induced proliferation and SCF-induced c-kit phosphorylation with I

5、C50of 207 nM and 37 nM, respectively, but not effective against the EGF-induced EGFR phosphorylation andcell viability of A431 cells 1. Althouth displaying little antiproliferative activity on cell growth of HUVECsalone, Motesanib treatment significantly sensitizes the cells to fractionated radiatio

6、n 2.体内研究 Motesanib (100 mg/kg) significantly inhibits VEGF-induced vascular permeability in a time-dependentmanner. Oral administration of Motesanib twice daily or once daily potently inhibits, in a dose-dependentmanner, VEGF-induced angiogenesis using the rat corneal model with ED50 of 2.1 mg/kg an

7、d 4.9 mg/kg,respectively. Motesanib induces a dose-dependent tumor regression of established A431 xenografts byselectively targeting neovascularization in tumor cells 1. Motesanib in combination with radiation displayssignificant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) x

8、enograft models2. Motesanib treatment also induces significant dose-dependent reductions in tumor growth and bloodvessel density of MCF-7, MDA-MB-231, or Cal-51 xenografts, which can be markedly enhanced whencombined with docetaxel or tamoxifen 3.PROTOCOLKinase Assay 1 Optimal enzyme, ATP, and subst

9、rate (gastrin peptide) concentrations are established for each enzyme usinghomogeneous time-resolved fluorescence (HTRF) assays. Motesanib is tested in a 10-point dose-responsecurve for each enzyme using an ATP concentration of two-thirds Km for each. Most assays consist ofenzyme mixed with kinase r

10、eaction buffer 20 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 5 mM MnCl2, 100 mMNaCl, 1.5 mM EGTA. A final concentration of 1 mM DTT, 0.2 mM NaVO4, and 20 g/mL BSA is addedbefore each assay. For all assays, 5.75 mg/mL streptavidin-allophycocyanin and 0.1125 nM Eu-PT66 areadded immediately before the HTRF rea

11、ction. Plates are incubated for 30 minutes at room temperature andread on a Discovery instrument. IC50 values are calculated using the Levenberg-Marquardt algorithm into afour-parameter logistic equation.MCE has not independently confirmed the accuracy of these methods. They are for reference only.C

12、ell Assay 1 Cells are preincubated for 2 hours with different concentrations of Motesanib, and exposed with 50 ng/mLVEGF or 20 ng/mL bFGF for an additional 72 hours. Cells are washed twice with DPBS, and plates arefrozen at -70C for 24 hours. Proliferation is assessed by the addition of CyQuant dye,

13、 and plates are read ona Victor 1420 workstation. IC50 data are calculated using the Levenberg-Marquardt algorithm into a four-parameter logistic equatio.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal A431 cells are cultured in DMEM (low glucose

14、) with 10% FBS and penicillin/streptomycin/glutamine. CellsAdministration 1 are harvested by trypsinization, washed, and adjusted to a concentration of 5107/mL in serum-free medium.Animals are challenged s.c. with 1107 cells in 0.2 mL over the left flank. Approximately 10 days thereafter,mice are ra

15、ndomized based on initial tumor volume measurements and treated with either vehicle (Ora-Plus)or Motesanib. Tumor volumes and body weights are recorded twice weekly and/or on the day of sacrifice.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemETumor volume is measured with a Pro-Max electronic digi

16、tal caliper and calculated using the formula length(mm)width (mm)height (mm) and expressed in mm3. Data are expressed as meanSE. Repeatedmeasures ANOVA followed by Scheffe post hoc testing for multiple comparisons is used to evaluate thestatistical significance of observed differences.MCE has not in

17、dependently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Cell Physiol Biochem. 2018;48(1):227-236. Oncotarget. 2016 Sep 27;7(39):63839-63855. Harvard Medical School LINCS LIBRARYSee more customer validations on H

18、YPERLINK / www.MedChemEREFERENCES1. Polverino A, et al. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derivedgrowth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer R2. Kruser TJ, et al. Augmentation of radiation re