Pamufetinib-mesylate-TAS-115-mesylate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPamufetinibmesylateCat.No.:HY-12423ACASNo.:1688673-09-7Synonyms:TAS-115mesylate分⼦式:C₂₈H₂₇FN₄O₇S₂分⼦量:614.66作⽤靶点:VEGFR;c-Met/HGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:75mg/mL(122.02mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6269mL8.1346mL16.2692mL5mM0.3254mL1.6269mL3.2538mL10mM0.1627mL0.8135mL1.6269mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.07mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.07mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Pamufetinib(TAS-115)mesylate⼀种有效的VEGFR和肝细胞⽣长因⼦受体(c-Met/HGFR)的靶向激酶抑制剂，能够抑制rVEGFR2和rMET的活性，IC50值分别为30和32nM。IC50&TargetIC50:30nM(rVEGFR2),32nM(rMET)[1]体外研究PamufetinibmesylatepowerfullysuppressestheVEGF-dependentproliferationofHUVECs(IC50=0.019μM)asaVEGFR-targetedinhibitorandpowerfullysuppressestheproliferationofMET-amplifiedcancercells(GI50=0.032-0.362μM)asaMET-targetedinhibitor.PamufetinibmesylatehasmuchlesstoxicityinvariousnormalcelllineswhencomparedwithotherVEGFR-targetedkinaseinhibitors[1].CrizotinibandPamufetinibmesylateinhibitMetphosphorylationandreverseerlotinibresistanceandVEGFproductiontriggeredbyHGFinPC-9andHCC827cells[2].体内研究PamufetinibmesylatecompletelysuppressestheprogressionofMET-inactivatedtumorbyblockingangiogenesiswithouttoxicitywhengiveneverydayfor6weeks,evenataserum-saturatingdoseofPamufetinibmesylate.PamufetinibmesylateinducesmarkedtumorshrinkageandprolongessurvivalinMET-amplifiedhumancancer–bearingmice[1].PROTOCOLCellAssay[2]Tumorcells(8000cells/800mL)withorwithoutTAS-115(1.0μM)orerlotinib(0.3μM)inthelowerTranswellcollagen–coatedchambersarecoculturedwithMRC-5(1000cells/300μL)cellsintheupperchamberfor72hours.Theupperchamberisthenremoved.CellviabilityismeasuredusingtheMTTassay[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]TheTAS-115doselevelsaresetat12.5,50,and200mg/kg/d.Thedoselevelforsunitinibissetat40mg/kg/d.Oraldrugtreatmentiscontinuedfor14or42consecutivedaysforthechronicdosingintheSC-9xenograftmodel.Duringthetreatmentperiod,TVandbodyweightaremeasuredtwiceperweek.Theantitumorefficacyisassessedattheendofeachstudyperiod[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].FujitaH,etal.ThenovelVEGFreceptor/MET-targetedkinaseinhibitorTAS-115hasmarkedinvivoantitumorpropertiesandafavorabletolerabilityprofile.MolCancerTher.2013Dec;12(12):2685-96.[2].NakadeJ,etal.TripleinhibitionofEGFR,Met,andVEGFsuppressesregrowthofHGF-triggered,erlotinib-resistantlungcancerharboringanEGFRmutation.JThoracOncol.2014Jun;9(6):775-83.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMcePdfHeightCaution:Produc