1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESAR131675Cat. No.: HY-15458CAS No.: 1433953-83-3分式: CHNO分量: 358.39作靶點: VEGFR作通路: Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 28 mg/mL (78.13 mM)* means solubl

2、e, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.7903 mL 13.9513 mL 27.9026 mL5 mM 0.5581 mL 2.7903 mL 5.5805 mL10 mM 0.2790 mL 1.3951 mL 2.7903 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 SAR131675是有效，選擇性的 VEGFR3 抑制劑，IC50 值為23 nM。IC50 & Target

3、VEGFR323 nM (IC50)體外研究AR131675 is highly selective for VEGFR-3 versus 107 receptors, enzymes, ion channels, and 65 kinases.1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEHowever, it is moderately active on VEGFR-2 with a VEGFR-3/VEGFR-2 ratio of about 10. SAR131675inhibits VEGFR-3 tyrosine kinase

4、activity and VEGFR-3 autophosphorylation in HEK cells with IC50 values of20 and 45 nM, respectively. SAR131675 dose dependently inhibits the proliferation of primary humanlymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC50 of about 20 nM.SSAR131675 has no antiproliferative

5、activity on a panel of 30 tumors and primary cells, further showing itshigh specificity and indicating that SAR131675 is not a cytotoxic or cytostatic agent 1.體內(nèi)研究 SAR131675 is very well tolerated in mice and shows a potent antitumoral effect in several orthotopic andsyngenic models, including mamma

6、ry 4T1 carcinoma and RIP1.Tag2 tumors. Interestingly, it significantlyreduces lymph node invasion and lung metastasis, showing its antilymphangiogenic activity in vivo.SAR131675 significantly reduces TAM infiltration and aggregation in 4T1 tumors 1.PROTOCOLKinase Assay 1 Multiwell plates are precoat

7、ed with a synthetic polymer substrate poly-Glu-Tyr (polyGT 4:1). The reaction iscarried out in the presence of kinase buffer (10: 50 mM HEPES buffer, pH 7.4, 20 mM MgCl2, 0.1 mMMnCl2, and 0.2 mM Na3VO4) supplemented with ATP and dimethyl sulfoxide (DMSO) for the positive control(C+) or SAR131675 (ra

8、nging from 3-1,000 nM). ATP is used at 30 M for VEGFR-1 and VEGFR-3 and at 15M for VEGFR-2. The phosphorylated poly-GT is probed with a phosphotyrosine specific monoclonalantibody (mAb) conjugated to horseradish peroxidase and developed in the dark with the HRP chromogenicsubstrate (OPD). The reacti

9、on is then stopped by the addition of 100 L 1.25 mol/L H2SO4, and absorbanceis determined using an Envision spectrophotometer at 492 nm 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 HLMVECs are seeded in 96-well plates coated with 0.3%

10、gelatin (5000 cells per well). Cells are incubated inRPMI 0.1% FCS with VEGFA (10 ng/mL) VEGFC (300 ng/mL), VEGFD (300 ng/mL), or FGF2 (10 ng/mL) inthe absence or presence of SAR131675. Five days later, viable cells are quantified with the cell Titer-gloluminescent cell viability assay 1.MCE has not

11、 independently confirmed the accuracy of these methods. They are for reference only.Animal Mouse: Sterile sponge disks impregnated with 200 g of FGF2 or PBS are subcutaneously introduced on theAdministration 1 back of anaesthetized mice. FGF2 is reinjected into the sponges the first 2 days. Daily or

12、al treatment withSAR131675 (30, 100, and 300 mg/kg/d) started the day of sponge implantation. Seven days later, theanimals are euthanatized and the sponges are removed, harvested, and lysed in RIPA buffer at 4C. After acentrifugation at 6,000 g, the supernatants are collected for further analysis 1.

13、MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Oncotarget. 2016 Sep 27;7(39):63839-63855.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Alam A, et al. SAR131675, a potent and selective VEGFR-3-TK inhibitor with antilymphangiogenic, antitumoral, and antimetastaticactivities. Mol Cancer Ther. 2012 Aug;11(8):1637-49.