Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECYM-5541Cat.No.:HY-101419CASNo.:945128-26-7Synonyms:ML249分?式:C??H??N?O?分?量:316.44作?靶點:LPLReceptor作?通路:GPCR/GProtein儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:25mg/mL(79.00mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.1602mL15.8008mL31.6016mL5mM0.6320mL3.1602mL6.3203mL10mM0.3160mL1.5801mL3.1602mL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；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(7.90mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.90mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.90mM);ClearsolutionBIOLOGICALACTIVITY?物活性CYM-5541(ML249)選擇性的S1P3受體變構(gòu)激動劑，EC50值在72?132nM之間。IC50&TargetEC50:between72and132nM(S1P3)[1]體外研究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