Lotamilast-RVT-501-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELotamilastCat.No.:HY-12740CASNo.:947620-48-6Synonyms:RVT-501;E6005分?式:C??H??N?O?分?量:472.49作?靶點(diǎn):Phosphodiesterase(PDE)作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:25mg/mL(52.91mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1164mL10.5822mL21.1645mL5mM0.4233mL2.1164mL4.2329mL10mM0.2116mL1.0582mL2.1164mL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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(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>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:2.5mg/mL(5.29mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Lotamilast(RVT-501;E6005)選擇性的磷酸?酯酶4(PDE4)抑制劑，IC50值為2.8nM。IC50&TargetIC50:2.8nM(humanPDE4)[1]體外研究LotamilastpotentlyandselectivelyinhibitshumanPDE4activitywithanIC50of2.8nMandsuppressestheproductionofvariouscytokinesfromhumanlymphocytesandmonocyteswithIC50valuesrangingfrom0.49to3.1nM[1].體內(nèi)研究Lotamilastiscurrentlyinphase2developmentforpatientswithmild-to-moderateatopicdermatitis.Inmicemodels,thetopicalapplicationofLotamilastproducesanimmediateantipruriticeffectaswellasananti-inflammatoryeffectwithreducedexpressionofcytokines/adhesionmolecules.Onthebasisoftheseobservedeffects,topicalRVT-501amelioratestheappearanceofatopicdermatitis-likeskinlesionsintwotypesofADmodels,hapten-andmite-elicitedmodels,exhibitinginhibitoryeffectscomparabletothatoftacrolimus[1].AsingletopicalapplicationofLotamilastsignificantlyinhibitsspontaneousscratchingduring1–2hafterapplicationinmicewithchronicdermatitis;theinhibitionispartialandsimilarbetween0.01%and0.03%.Topicalapplicationof0.03%Lotamilasttotherostralbacksignificantlyinhibitstheincreasedactivityofthecutaneousnerveinmicewithchronicdermatitis.ThecutaneousconcentrationofcAMPissignificantlydecreasedinmicewithchronicdermatitis,andthisdecreaseisreversedbytopicalLotamilastapplication[2].PROTOCOLKinaseAssay[1]PDEisoenzymeactivitiesarequantifiedbymeasuringtheformationof[3H]5′-AMPor[[3H]5′-GMPfrom[[3H]cAMPor[[3H]cGMPusinganenzymeisolatedfrombovinebrain(forPDE1),differentiatedU-937cells(forPDE2),humanplatelets(forPDE3andPDE5),andU-937cells(forPDE4).Thetestcompounds(RVT-501),referencecompounds,orvehicle(water)isaddedtoareactionbuffer.Thereactionisinitializedbyadditionoftheenzyme,andthemixtureisincubatedfor60minutesat22°C.Afterincubation,thereactionisstoppedbyheatingtheplateto60°Cfor3minutes,afterwhichtimescintillationproximityassaybeadsareadded.After20minutesofshakingat22°C,theamountof[[3H]5′-AMPor[[3H]5′-GMPisquantifiedwithascintillationcounters[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Lotamilastisappliedtothehair-clippedrostralback.Observationofhind-pawscratchingandAdministration[2]electrophysiologicalrecordingofthecutaneousnervebranchareconducted.TheeffectsoftopicalapplicationofE6005areevaluated1hafterapplication,becausetopicalapplicationofthevehicleelicitedhind-pawscratchingfor40min.ThecutaneousconcentrationofcAMPismeasuredbyenzymeimmunoassay[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].IshiiN,etal.Antipruriticeffectofthetopicalphosphodiesterase4inhibitorE6005amelioratesskinlesionsinamouseatopicdermatitismodel.JPharmacolExpTher.2013Jul;346(1):105-12.[2].AndohT,etal.TopicalE6005,anovelphosphodiesterase4inhibitor,attenuatesspontaneousitch-relatedresponsesinmicewithchronicatopy-likedermatitis.ExpDermatol.2014May;23(5):