IBMX-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEIBMXCat.No.:HY-12318CASNo.:28822-58-4分?式:C??H??N?O?分?量:222.24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:100mg/mL(449.96mM;Needultrasonic)掃描?維碼，Ethanol:≥7.14mg/mL(32.13mM)運(yùn)?溶解?案計(jì)算器*"≥"meanssoluble,butsaturationunknown.獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲備液1mM4.4996mL22.4982mL44.9964mL5mM0.8999mL4.4996mL8.9993mL10mM0.4500mL2.2498mL4.4996mL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，并請注意儲備液的保存?式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(11.25mM);Clearsolution此?案可獲得≥2.5mg/mL(11.25mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。1/4www.MedChemEwww.MedChemE2.請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.25mM);Clearsolution此?案可獲得≥2.5mg/mL(11.25mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.5mg/mL(11.25mM);Clearsolution此?案可獲得≥2.5mg/mL(11.25mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個?以上的實(shí)驗(yàn)。4.以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL??油中，混合均勻。請依序添加每種溶劑：10%EtOH40%PEG3005%Tween-8045%salineSolubility:≥0.71mg/mL(3.19mM);Clearsolution此?案可獲得≥0.71mg/mL(3.19mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL7.1mg/mL的澄EtOH儲備液加到400μLPEG300中，混合均勻；向上述體5.系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%EtOH90%(20%SBE-β-CDinsaline)Solubility:≥0.71mg/mL(3.19mM);Clearsolution此?案可獲得≥0.71mg/mL(3.19mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL7.1mg/mL的澄EtOH儲備液加到900μL20%的SBE-β-CD?理鹽??溶液6.中，混合均勻。請依序添加每種溶劑：10%EtOH90%cornoilSolubility:≥0.71mg/mL(3.19mM);Clearsolution此?案可獲得≥0.71mg/mL(3.19mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL7.1mg/mL的澄EtOH儲備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性IBMX?種?譜的磷酸?酯酶(PDE)抑制劑，抑制PDE3，PDE4和PDE5，IC50分別為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]體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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