Emricasan-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEEmricasanCat.No.:HY-10396CASNo.:254750-02-2分?式:C??H??F?N?O?分?量:569.5作?靶點:Caspase;InfluenzaVirus作?通路:Apoptosis;Anti-infection儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥42mg/mL(73.75mM)掃描?維碼，*"≥"meanssoluble,butsaturationunknown.運?溶解?案計算器獲得適合您實驗體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7559mL8.7796mL17.5593mL5mM0.3512mL1.7559mL3.5119mL10mM0.1756mL0.8780mL1.7559mL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。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(4.39mM);Clearsolution此?案可獲得≥2.5mg/mL(4.39mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。1/4www.MedChemEwww.MedChemE2.請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.39mM);Clearsolution此?案可獲得≥2.5mg/mL(4.39mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.5mg/mL(4.39mM);Clearsolution此?案可獲得≥2.5mg/mL(4.39mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性Emricasan(PF03491390)?種?服有效的不可逆pan-caspase抑制劑。Emricasan抑制Zika病毒(ZIKV)誘導(dǎo)的caspase-3活性增加并保護了?類?層神經(jīng)祖細胞[1]。IC50&TargetCaspase體外研究Emricasan(PF03491390;IDN-6556)(50μM;24hours)directlyimproveshepatocytesphenotypeinprimaryratcirrhotichepatocytes[1].Emricasan(10-50μM)hashepatoprotectiveeffectsinhumanlivercells[1].體內(nèi)研究Emricasan(PF03491390;IDN-6556)isorallyactivethatisretainedintheliverforprolongedperiodoftime.TUNEL-positivecellsareconsiderablyincreasedbyfive-foldinmicefedaHFDandarereducedunderEmricasantreatment.Inaccordancewiththisobservationcaspase-3and-8areincreasedinHFD-fedmiceby1.5-and1.3-foldrespectivelyandaresignificantlydecreasedbyEmricasantreatment[2].Whencomparingefficacybymultipleroutesofadministration,Emricasanisadministeredi.p.,p.o.,i.m.,ori.v.(0.03-3mg/kg).Caspase3-likeactivities,measuredasDEVD-AMCcleavage,dosedependentlydecreasedwitha92.5%reductionafterthehighestdoseofEmricasan(3mg/kg).Emricasanisinitiallytestedintheα-Fasmodelofliverinjury,markedhepatocellularapoptosis,andpeakALTactivitieswithin6h.Emricasanisadministeredi.p.immediatelyafteradministrationofα-Fas,ALTactivities,measured6hlater,decreasedinadose-dependentmannerwithanED50valueof0.08(0.06-0.12)mg/kg[3].Emricasanisahighlyselectivepan-caspaseinhibitordemonstratingirreversibleinhibitionandasignificantfirst-passeffect.Inbothsyngeneicmouseisletsandhumanisletstransplantedintoimmunodeficientmice,Emricasan(i.p.,20mg/kg)givenfor7dayspost-transplantledtoasignificantlyenhancedrateofdiabetesreversalascomparedtovehicle[4].PROTOCOLAnimalMice[2]Administration[2][3]ThemaleC57BL/6Jmiceareage-matchedandusedatapproximately12-16weeksofage.Fourgroupsarestudied(n=60)with15micepergroup.Groups1and3receiveregularchow.Groups2and4receiveHFDand50g/L(Sucrose)isaddedtodrinkingwaterfor20weeks.Groups3and4receiveEmricasan0.32/4www.MedChemEwww.MedChemEmg/kg/dayperos,andGroup1and2receivethevehicle.TheoraladministrationofEmricasanatdosesof0.3mg/kgcorrespondstotheED90valuetopreventliverinjuryinthemodelofα-Fas-inducedliverinjury.Totalbodyweightismeasuredat0,5,10,15and20weeks.Rats[3]ThemaleSprague-Dawleyratsareused.Blood(100μL/sample)istakenfromthecarotidcannula2to240minafteradministrationofEmricasan(i.v.,s.c.,p.o.,ori.p.).Serumispreparedandfrozenimmediatelyuntilanalysis.Instudiesmeasuringdrugconcentrationsinportalandsystemicblood,individualratsarebled(threeanimalspertimepoint)simultaneouslyfromtheportalveinandinferiorvenacava.Inthebiliaryexcretionstudy,bileiscollectedfromthecommonbileductafteri.v.andp.o.administrationofEmricasan(10mg/kg)overa24-hperiodoniceandfrozenuntilanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?Nature.2019Nov;575(7784):683-687.?SciTranslMed.2016May18;8(339):339ra69.?JExpMed.2018Jul2;215(7):1839-1852.?NatProtoc.2015May;10(5):807-21.?CellRep.2020Jan28;30(4):1260-1270.e5.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BarreyroFJ,etal.Thepan-caspaseinhibitorEmricasan(IDN-6556)decreasesliverinjuryandfibrosisinamurinemodelofnon-alcoholicsteatohepatitis.LiverInt.2015Mar;35(3):953-66.[2].HoglenNC,etal.CharacterizationofIDN-6556(3-[2-(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoicacid):aliver-targetedcaspaseinhibitor.JPharmacolExpTher.2004May;309(2):634-40.[3].McCallM,etal.ThecaspaseinhibitorIDN-6556(PF3491390)improvesmarginalmassengraftmentafterislettransplantationinmice.Surgery.2011Jul;150(1):48-55.[4].TianJ,etal.CombinationofEmricasanwithAP24534SynergisticallyReducesIschemia/ReperfusionInjuryinRatBrainThroughSimultaneousPreventionofApoptosisandNecroptosis.TranslStrokeRes.2017Nov4.[5].Gracia-SanchoJ,etal.EmricasanAmelioratesPortalH