CYM-5541-ML249-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECYM-5541Cat.No.:HY-101419CASNo.:945128-26-7Synonyms:ML249分⼦式:C₁₉H₂₈N₂O₂分⼦量:316.44作⽤靶点:LPLReceptor作⽤通路:GPCR/GProtein储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:25mg/mL(79.00mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.1602mL15.8008mL31.6016mL5mM0.6320mL3.1602mL6.3203mL10mM0.3160mL1.5801mL3.1602mL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。-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>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(7.90mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.90mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.90mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性CYM-5541(ML249)选择性的S1P3受体变构激动剂，EC50值在72⾄132nM之间。IC50&TargetEC50:between72and132nM(S1P3)[1]体外研究CYM-5541isafullagonist,abletoreachthemaximumlevelofERKphosphorylationthatisobservedwithS1P.CYM-5541hasanEC50ofbetween72and132nMandexhibitsexquisiteselectivityoverotherS1Preceptorsubtypes:S1P1EC50>10μM,S1P2EC50>50μM,S1P4EC50>50μM,andS1P5EC50>25μM.CYM-5541alsoshowsselectivityoveralargepanelofproteintargets,withnosignificantactivities,intheRicercaprofilingpanelof55GPCRs,ionchannels,andtransporters.CYM-5541allowedustoidentifyanallostericsitewhereF263isakeygate-keeperresidueforitsaffinityandefficacy.ThenovelallosterichydrophobicpocketmayaccountfortheS1P3selectivityofCYM-5541[1].PROTOCOLKinaseAssay[1]Jump-InTICHO-KcellsstablyexpressingWTormutantS1P3areserum-starvedfor4hrs.Theyarethenincubatedat4°Cfor30mininthebindingbuffercontaining20mMTris-HCl(pH7.5),100mMNaCl,15mMNaF,0.5mMEDTA,1mMNa3VO4,0.5%fattyacid-freebovineserumalbumin,andproteaseinhibitormixturewith0.1nM[33P]S1PandincreasingconcentrationsofS1P,SPM-242,orCYM-5541.Cellsarewashedthreetimeswithcoldbindingbuffer.Cell-boundradioactivityismeasuredbylysingthecellswith0.5%SDSfollowedbyliquidscintillationcounting.Therawdataisnormalizedsothatthelevelof[33P]S1Pboundtoeachcellline(WTormutant)intheabsenceofcompetingligandisreferencedas100%foritsowncellline[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].JoE,etal.NovelselectiveallostericandbitopicligandsfortheS1P(3)receptor.ACSChemBiol.2012Dec21;7(12):1975-83.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor