Bisindolylmaleimide-I-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEBisindolylmaleimideICat.No.:HY-13867CASNo.:133052-90-1分⼦式:C₂₅H₂₄N₄O₂分⼦量:412.48作⽤靶点:PKC作⽤通路:Epigenetics;TGF-beta/Smad储存⽅式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfromlight)溶解性数据体外实验DMSO:≥32mg/mL(77.58mM)扫描⼆维码，*"≥"meanssoluble,butsaturationunknown.运⽤溶解⽅案计算器获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4244mL12.1218mL24.2436mL5mM0.4849mL2.4244mL4.8487mL10mM0.2424mL1.2122mL2.4244mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存⽅式和期限。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶1.请依序添加每种溶剂：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥1mg/mL(2.42mM);Clearsolution此⽅案可获得≥1mg/mL(2.42mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL10.0mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。1/3www.MedChemEwww.MedChemEBIOLOGICALACTIVITY⽣物活性BisindolylmaleimideI(GF109203X)⼀种⾼度选择，可渗透细胞，可逆的PKC抑制剂，Ki值为14nM。IC50&TargetBovinebrainPKCPKCβIIPKCβIPKCα10nM(IC50)16nM(IC50)17nM(IC50)20nM(IC50)PKCγFDGFR20nM(IC50)65μM(IC50)体外研究BisindolylmaleimideIisacompetitiveinhibitorwithrespecttoATP(Ki=14nM)anddisplayshighselectivityforPKCascomparedtofivedifferentproteinkinases.GF109203XefficientlypreventsPKC-mediatedphosphorylationsofanMr=47,000proteininplateletsandofanMr=80,000proteininSwiss3T3cells.GF109203Xinhibitscollagen-anda-thrombin-inducedplateletaggregationaswellascollagen-triggeredATPsecretion.However,ADP-dependentreversibleaggregationisnotmodified.InSwiss3T3fibroblasts,GF109203Xreversestheinhibitionofepidermalgrowthfactorbindinginducedbyphorbol12,13-dibutyrateandprevents[3H]thymidineincorporationintoDNA,onlywhenthisiselicitedbygrowthpromotingagentswhichactivatePKC[1].体内研究Pialarteriolediameterchangesaremonitoredusingaclosedcranialwindowinvivomicroscopytechnique.ThepialarterioledilatoryresponseassociatedwithSNSisdecreasedby45%,whencomparingDMvseitherNDorTRrats.Also,pialarteriolardilationstotopicalKClandNS1619arelargelyattenuatedinDMrats,butnotinNDorTRanimals.TheseresponsesarecompletelyrestoredbytheacuteapplicationofBisindolylmaleimideItothebrainsurface.ThePKCinhibitorhasnoeffectonvascularresponsesinnormoglycemicandTRanimals.Inconclusion,DM-associatedchronicimpairmentofneurovascularcouplingmaybereadilyreversedbyaPKC-α/β/γinhibitororpreventedviapancreaticislettransplantation.SpecificPCKisoforms(α/β/γ)arebelievedtobemechanisticallylinkedtotheneurovascularuncouplingseenwithhyperglycemia[2].PROTOCOLKinaseAssay[1]AssayofPKCisarrayedbymeasuring32Pitransferredfrom[γ-32Pi]ATPtolysine-richhistonetypeIll-s.Thereactionmixture(80μL)contains50mMTris-HCI,pH7.4.100μMCaCl2,10mMMgCI2,37.5μg/mLhistonetypeIll-s,l0μM[γ-32Pi]ATP(1250cpm/pmol),31μMbovinebrainphosphatidylserineand0.5μM1,2sn-dioleylglycerol.15μLofpurifiedPKC(finalconcentrationinassay0.38μg/mL)isaddedtotheincubationmixture.After10minutes,thereactionisstoppedbyadditionofat30μLofcasein30mg/mLand0.9mLof12%trichlomaceticacid[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalThreesetsofLewisratsisusedforthisstudy:1)euglycemic4–6montholdnon-diabeticcontrols(NDgroup,Administration[2]n=11);2)streptozotocin(STZ)-treateddiabeticrats(6monthold,4monthspost-STZ)(DMgroup,n=6);and3)STZ-treateddiabeticanimals,subjectedtopancreaticislettransplantationsoonaftertheestablishmentofthediabeticmodel,studied100–110daysafterthetransplant(TRgroup,n=7)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3www.MedChemEwww.MedChemE户使⽤本产品发表的科研⽂献•Theranostics.2021Mar11;11(11):5279-5295.•Elife.2021Mar3;10:e60889.•JNutrBiochem.2020Nov26;108555.•FoodChemToxicol.2020Dec28;148:111925.•FoodChemToxicol.2019Mar;125:46-54.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ToullecD,etal.ThebisindolylmaleimideGF109203XisapotentandselectiveinhibitorofproteinkinaseC.JBiolChem.1991Aug25;266(24):15771-81.[2].VetriF,etal.ImpairmentofneurovascularcouplinginType1DiabetesMellitusinratsispreventedbypancreaticislettransplantationandreversedbyasemi-selectivePKCinhibitor.BrainRes.2017Jan15;1655:48-54.McePdfHeight关注MCE中国公众号，

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