Ro-31-8220-mesylate-Ro-31-8220-methanesulfonate-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERo31-8220mesylateCat.No.:HY-13866CASNo.:138489-18-6Synonyms:Ro31-8220methanesulfonate;BisindolylmaleimideIXmesylate分?式:C??H??N?O?S?分?量:553.65作?靶點:PKC作?通路:Epigenetics;TGF-beta/Smad儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:35.71mg/mL(64.50mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.8062mL9.0310mL18.0620mL5mM0.3612mL1.8062mL3.6124mL10mM0.1806mL0.9031mL1.8062mL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,awayfrommoisture)。-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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.76mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.76mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ro31-8220mesylate?種有效的PKC抑制劑，抑制PKCα，PKCβI，PKCβII，PKCγ，PKCε和???腦PKC的IC50值為5，24，14，27，24和23nM，也可抑制MAPKAP-K1b，MSK1，S6K1和GSK3β，IC50為3，8，15，38nM。IC50&TargetPKC-αPKC-βIPKC-βIIPKC-γ5nM(IC50)24nM(IC50)14nM(IC50)27nM(IC50)PKC-εRatBrainPKCMAPKAP-K1bMSK124nM(IC50)23nM(IC50)3nM(IC50)8nM(IC50)S6K1GSK3β15nM(IC50)38nM(IC50)體外研究Ro31-8220mesylateisapotentPKCinhibitor,withIC50sof5,24,14,27,24and23nMforPKCα,PKCβI,PKCβII,PKCγ,PKCεandratbrainPKC,respectively[1].Ro31-8220alsosignificantlyinhibitsMAPKAP-K1b,MSK1,S6K1andGSK3β(IC50s,3,8,15,and38nM,respectively),withnoeffectonMKK3,MKK4,MKK6andMKK7.Moreover,Ro31-8220directlysuppressesvoltage-dependentNa+channels[2].Ro31-8220(1μM)isneuroprotectiveagainstparaoxon-inducedneuronalcelldeathincerebellargranuleneurons,blocksparaoxon-inducedcaspase-3activity,andreducestheparaoxon-inducedincreaseinphospho-PKCpanlevels[3].體內(nèi)研究Ro31-8220(6mg/kg/d,s.c.)iswelltolerated,andhashalf-lifeof5.7hoursinmice.Ro31-8220-treatedMLP?/?miceshowadramaticrescueinfractionalshorteningaftertreatmentfor6weeks,buttheWTmiceshowsnochange[4].PROTOCOLCellAssay[1]Aneurotoxicconcentrationofparaoxon(200μM)isaddedtothegranulecellculturesfortheindicatedtimeondayinvitro(DIV)8.ThefollowingdrugsareaddedtothegranulecellculturespriortoorafterparaoxonexposureonDIV8:Ro-81-3220(1μM)isadded15minpriortoor3haftertheadditionofparaoxon.TPA(0.1μM)isadded15minpriortotheadditionofparaoxon[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[4]Administration[4]Theaffectsoflong-termRo31-8220administrationover4to6weeksinMLP?/?heartfailuremiceareinvestigated.Allmiceareassessedforventricularperformancebyechocardiographyatthebeginningofthe2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEstudyand6weekslater.Ro31-8220(orvehicle)isinjectedsubcutaneouslyonceperdayatadosageof6mg/kg/d[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?JClinInvest.2021Dec29;e150101.?NatCommun.2018Sep11;9(1):3688.?AgingCell.2022Feb23;e13573.?AgingCell.2020Oct;19(10):e13217.?FrontImmunol.2021Feb2;11:625542.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WilkinsonSE,etal.Isoenzymespecificityofbisindolylmaleimides,selectiveinhibitorsofproteinkinaseC.BiochemJ.1993Sep1;294(Pt2):335-7.[2].DaviesSP,etal.Specificityandmechanismofactionofsomecommonlyusedproteinkinaseinhibitors.BiochemJ.2000Oct1;351(Pt1):95-105.[3].TianF,etal.InhibitionofproteinkinaseCprotectsagainstparaoxon-mediatedneuronalcelldeath.Neurotoxicology.2007Jul;28(4):843-9.Epub2007Apr20.[4].HambletonM,etal.Pharmacological-andgenetherapy-basedinhibitionofproteinkinaseCalpha/betaenhancescardiaccontractilityandattenuatesheartfailure.Circulation.2006Aug8;1