Enpatoran-hydrochloride-M5049-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEnpatoranhydrochlorideCat.No.:HY-134581ACASNo.:2101945-93-9Synonyms:M5049hydrochloride分?式:C??H??ClF?N?分?量:356.77作?靶點(diǎn):Toll-likeReceptor(TLR)作?通路:Immunology/Inflammation儲存?式:-20°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:16.67mg/mL(46.72mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8029mL14.0146mL28.0293mL5mM0.5606mL2.8029mL5.6059mL10mM0.2803mL1.4015mL2.8029mL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(sealedstorage,awayfrommoistureandlight)。-80°C儲存時，請?jiān)?個?內(nèi)使?，-20°C儲存時，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)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(shí)驗(yàn)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(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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2mg/mL(5.61mM);Clearsolution;Needultrasonic1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2mg/mL(5.61mM);Clearsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:2mg/mL(5.61mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Enpatoran(M5049)hydrochloride?種有效的、具有?服活性的TLR7/8抑制劑，在HEK293細(xì)胞中，其IC50s分別為11.1nM和24.1nM。Enpatoranhydrochloride對TLR3,TLR4和TLR9?活性。Enpatoranhydrochloride可以阻斷分?合成配體和天然內(nèi)性RNA配體。Enpatoranhydrochloride在體內(nèi)的表現(xiàn)出良好的藥代動?學(xué)特性。Enpatoranhydrochloride可?于先天性和適應(yīng)性??免疫阻斷的相關(guān)研究。IC50&TargetTLR7TLR811.1nM(IC50)24.1nM(IC50)體外研究Enpatoranhydrochloride(0.01nM-10μM)inhibitsproductionofIL-6stimulatedbyalltheligands(miR-122,Let7cRNA,AluRNA,andR848)withIC50valuesrangingfrom35to45nM[1].體內(nèi)研究Pre-treatmentwithEnpatoranhydrochloride(oralgavage;1mg/kg)beforeR848(intraperitonealinjectionof25μg)dose-dependentlyinhibitstheproductionofIL-6andIFN-αinmice[1].Enpatoranhydrochlorideexhibitshighoralbioavailability(mouse100%,rat87%,dog84%)followingoraladministration(mouse,ratanddog1.0mg/kg)[1].Enpatoranhydrochlorideexhibitsmoderatehalf-lives(mouse1.4,rat5.0anddog13h)duetohighplasmaclearance(1.4,1.2and0.59L/h/kg,respectively)combinedwithlargevolumesofdistribution(2.7,8.7and5.7L/kg,respectively)followingintravenousadministration(mouse,ratanddog1.0mg/kg)[1].AnimalModel:FemaleC57BL/6mice[1]Dosage:0.1mg/kgand1mg/kgAdministration:Oralgavage;administered1hourpriortoR848challengeResult:TheTLR7/8agonistR848stimulatedbothIFN-αandIL-6productioninmice.EnpatoranhydrochloridedecreasedIFN-αandIL-6productionstimulatedbyR848.REFERENCES[1].JaromirVlach,etal.DiscoveryofM5049:ANovelSelectiveTLR7/8InhibitorforTreatmentofAutoimmunity.JPharmacolExpTher.2020Dec16;JPET-AR-2020-000275.McePdfHeightCaution:Producthasnotbeenfullyvalidate