IBMX-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEIBMXCat.No.:HY-12318CASNo.:28822-58-4分⼦式:C₁₀H₁₄N₄O₂分⼦量:222.24作⽤靶点:Phosphodiesterase(PDE)作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(449.96mM;Needultrasonic)扫描⼆维码，Ethanol:≥7.14mg/mL(32.13mM)运⽤溶解⽅案计算器*"≥"meanssoluble,butsaturationunknown.获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM4.4996mL22.4982mL44.9964mL5mM0.8999mL4.4996mL8.9993mL10mM0.4500mL2.2498mL4.4996mL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:≥2.5mg/mL(11.25mM);Clearsolution此⽅案可获得≥2.5mg/mL(11.25mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/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。1/4www.MedChemEwww.MedChemE2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.25mM);Clearsolution此⽅案可获得≥2.5mg/mL(11.25mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶3.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.5mg/mL(11.25mM);Clearsolution此⽅案可获得≥2.5mg/mL(11.25mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。4.以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。请依序添加每种溶剂：10%EtOH40%PEG3005%Tween-8045%salineSolubility:≥0.71mg/mL(3.19mM);Clearsolution此⽅案可获得≥0.71mg/mL(3.19mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL7.1mg/mL的澄EtOH储备液加到400μLPEG300中，混合均匀；向上述体5.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。请依序添加每种溶剂：10%EtOH90%(20%SBE-β-CDinsaline)Solubility:≥0.71mg/mL(3.19mM);Clearsolution此⽅案可获得≥0.71mg/mL(3.19mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL7.1mg/mL的澄EtOH储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶液6.中，混合均匀。请依序添加每种溶剂：10%EtOH90%cornoilSolubility:≥0.71mg/mL(3.19mM);Clearsolution此⽅案可获得≥0.71mg/mL(3.19mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL7.1mg/mL的澄EtOH储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性IBMX⼀种⼴谱的磷酸⼆酯酶(PDE)抑制剂，抑制PDE3，PDE4和PDE5，IC50分别为6.5，26.3和31.7μM。IC50&TargetIC50:6.5±1.2μM(PDE3),26.3±3.9μM(PDE4),31.7±5.3μM(PDE5)[1]体外研究At100μM,KMUP-1(axanthinederivative)andIBMXarethemosteffectiveatinducingtrachealrelaxation;themagnitudeoftherelaxationresponsesinducedbyKMUP-1andIBMXarenotsignificantlydifferent[1].IBMX(100μM)activatesrenaloutermedullaryK+(ROMK)channels(n=6,P<0.05)andpreventsfurtherchannelactivationbyANGII(n=6,P=NS)orcGMP.Ofnoteisthatpretreatmentofcorticalcollectingduct(CCDs)isolatedfromhigh-K+(HK)-fedratswithIBMX(100μM)for20minleadstoasignificantincreaseintubularcAMPcontentto1.43±0.35pg/mmtubulelength(n=14)comparewiththatmeasuredinvehicle-treatedcontrols(0.61±0.13pg/mmtubulelength,n=12,P<0.05)[2].体内研究IBMX,anon-selectivePDEinhibitorsignificantlydecreasestheliverglycogenstorage(mg/g,IBMX22±1.5P<0.001).Incomparisonwiththecontrolgroup,IBMXandmc5significantlyincreaseplasmaglucose(bloodglucose,mg/dl,control=141±3,IBMX=210±17P<0.001andmc5=191±13P<0.01)whileothertest2/4www.MedChemEwww.MedChemEcompounds(mc1,mc6,MCPIPandWin47203)donotproducesignificanteffect(control=141±3,mc1160±7,mc6175±9,MCPIP179±8andWin47203116±2P>0.05)alsomc2doesnotchangeplasmaglucose(control=141±3andmc2=145±5).IBMXhasthehighestefficacyonincreasingplasmaglucose[3].TreatmentswithIBMXandApocyninsignificantlydecreasecold-inducedelevationofrightventricular(RV)systolicpressure(23.5±1.8and24.2±0.6mmHg,respectively)althoughtheydonotdecreaseRVpressuretothewarmcontrollevels.IBMXorApocyninsignificantlyreducesmediallayerthickness(19.0±0.9,and16.9±0.8μm,respectively)andincreaseslumendiameter(62.7±4.2,and59.5±4.3μm,respectively)ofsmallPAsincold-exposedrats[4].PROTOCOLCellAssay[2]Cellsaregrownin24-wellplates105cellsperwell.Atconfluence,monolayercellsarewashedwithphosphatebuffersolution(PBS)andthenincubatedwithKMUP-1(0.1-100μM)inthepresenceof100μMIBMXfor20min.Incubationisterminatedbytheadditionof10%trichloroaceticacid(TCA).Cellsuspensionsaresonicatedandthencentrifugedat2500×gfor15minat4°C.ToremoveTCA,thesupernatantsareextractedthreetimeswith5volumesofwater-saturateddiethylether.Then,thesupernatantsarelyophilizedandthecyclicGMPorAMPofeachsampleisdeterminedbyusingcommerciallyavailableradioimmunoassaykits[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3][4]Malemice(25-35g)areused.Fortheexperiment,thetestcompound(IBMX,MCPIP,mc1,mc2,mc5ormc6)orsolvent(control)isinjectedsubcutaneouslytomiceat1mg/kgdosagetwiceaday(8:00a.m.and8:00p.m.)for7days.Rats[4]SixgroupsofmaleSprague-Dawleyratsareused(150-180g,6rats/group).Threegroupsofratsareexposedtoaclimate-controlledwalk-inchambermaintainedatmoderatecold(5.0±1°C).Theremaininggroupsarekeptinanidenticalchambermaintainedatroomtemperature(23.5±1°C,warm)andservedascontrols.Aftereightweeksofexposuretocold,3groupsineachtemperatureconditionreceivedcontinuousIVinfusionofIBMX(PDE-1inhibitor,8.5mg/kg/day),Apocynin(NADPHoxidaseinhibitor,25mg/kg/day)andvehicle(DMSO,50%),respectively.ThedosesofdrugshavebeenvalidatedforeffectiveinhibitionofPDE-1andNADPHoxidaseactivity,respectively.Bodyweightismeasuredweekly.Afteroneweekofdruginfusion,theanimals’rightventricularsystolicbloodpressure(RVBP)ismeasuredunderanesthesia.TheRVPisareliableindicatorofpulmonaryarterialbloodpressure(PAP)andhasbeenusedbynumerousinvestigatorsforevaluatingPH.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CarbohydrPolym.2019Apr1;209:363-371.•FreeRadicBiolMed.2018Jun;121:215-230.•JCellPhysiol.2021Apr14.•JCellBiochem.2019Jan;120(1):321-331.3/4www.MedChemEwww.MedChemE•Patent.US20180263995A1.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WuBN,etal.KMUP-1,axanthinederivative,inducesrelaxationofguinea-pigisolatedtrachea:theroleoftheepithelium,cyclicnucleotidesandK+channels.BrJPharmacol.2004Aug;142(7):1105-14[2].WeiY,etal.AngiotensinIItype2receptorregulatesROMK-likeK+chann