RIPA-56-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERIPA-56Cat.No.:HY-101032CASNo.:1956370-21-0分?式:C??H??NO?分?量:221.3作?靶點(diǎn):RIPkinase作?通路:Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥100mg/mL(451.88mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM4.5188mL22.5938mL45.1875mL5mM0.9038mL4.5188mL9.0375mL10mM0.4519mL2.2594mL4.5188mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(11.30mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.30mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(11.30mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.75mg/mL(12.43mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.75mg/mL(12.43mM);ClearsolutionBIOLOGICALACTIVITY?物活性RIPA-56?種?效選擇和代謝穩(wěn)定的受體相互作?蛋?1(RIP1)抑制劑，IC50為13nM。RIPA-56可?于研究全?炎癥反應(yīng)綜合征[1]。IC50&TargetIC50:13nM(RIP1)[1]體外研究RIPA-56showsefficientinhibitionofRIP1kinaseactivity,withanIC50of13nMandnoinhibitionofRIP3kinaseactivityata10μMconcentration.RIPA-56alsodemonstratespotencyinprotectionofmurineL929cellsfromTNFα/z-VAD-FMK(TZ)-inducednecrosis(EC50=27nM)[1].體內(nèi)研究IntheSIRSmicediseasemodel,RIPA-56efficientlyreducestumornecrosisfactoralpha(TNFα)-inducedmortalityandmulti-organdamage.ComparedtoknownRIP1inhibitors,RIPA-56ispotentinbothhumanandmurinecells,ismuchmorestableinvivo,andisefficaciousinanimalmodelstudies.RIPA-56hasanimpressivePKprofileinmicewitha3.1hhalf-life,22%oralbioavailability(P.O.),and100%bioavailabilityfromintraperitonealinjection(I.P.)[1].PROTOCOLCellAssay[1]Cellnecrosisassayisperformedin96-wellcellcultureplate.3,000cellsareplatedineachwellandculturedat37°Covernight.HT-29cellsaretreatedwith20ng/mLTNFα/100nMSmacMimetics/20μMz-VAD-FMKandRIPA-56for24h.L929cellsaretreatedwith20ng/mLTNFα/20μMz-VAD-FMKandRIPA-56for6h.ThecellsurvivalratioisdeterminedusingtheCellTiter-GloLuminescentCellViabilityAssaykit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Followingintraveneous(IV),intraperitoneal(IP),ororaladministration(PO)ofRIPA-56toC57BL/6Administration[1]mice(n=3),bloodissampledthrougheyepunctureatvarioustimepoints.CompoundconcentrationsintheplasmasamplesareanalyzedbyLCMS/MS.Pharmacokineticparametersaredeterminedfromindividualanimaldatausingnoncompartmentalanalysisinphoenix64[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?StemCellsDev.2020Apr15;29(8):475-487.?Patent.US20220362179A1.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RenY,etal.DiscoveryofaHighlyPotent,Selective,andMetabolicallyStableInhibitorofReceptor-InteractingProtein1(RIP1)fortheTreatmentofSystemicInflammatoryResponseSyndrome.JMedChem.2017Feb9;60(3):972-986.McePdfHeightCaution:Pr