TG100-115-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETG100-115Cat.No.:HY-10111CASNo.:677297-51-7分⼦式:C₁₈H₁₄N₆O₂分⼦量:346.34作⽤靶点:PI3K作⽤通路:PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:33.33mg/mL(96.23mM;ultrasonicandwarmingandadjustpHto2withHClandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8873mL14.4367mL28.8734mL5mM0.5775mL2.8873mL5.7747mL10mM0.2887mL1.4437mL2.8873mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。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%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(7.22mM);Clearsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(7.22mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性TG100-115⼀种选择性的PI3Kγ/PI3Kδ抑制剂，IC50分别为83和235nM。IC50&TargetPI3KδPI3Kγ235nM(IC50)83nM(IC50)体外研究TG100-115inhibitsPI3KγandPI3KδwithIC50sof83and235nM,respectively,whereasbothPI3KαandPI3Kβarerelativelyunaffected(IC50values>1μM).Asagaugeofgeneralspecificity,TG100-115isalsoassayedagainsta133proteinkinasepanel,noneofwhichareinhibitedatIC50values[1].体内研究Tocorrelatetheseinvivoresponseswiththemoleculartargetofinterest,PI3KpathwaysignalingismonitoredthroughwesternblotanalysesofAktphosphorylation(aPI3K-mediatedevent).VEGFinjectioni.v.inmiceinducesarapidAktphosphorylationreadilydetectableinlunglysates,pretreatmentwithTG100-115blocksthisresponse.BlockadeisseenwithTG100-115dosesaslowas0.5mg/kgandpersistsoveraperiodofseveralhours.Ininitialdose-rangingstudies,generallyequivalentresponsesareobservedusingTG100-115dosesof0.5-10mg/kg,andwethereforeelectedtoconductastatisticallypoweredtestatthelowestdose.AnimalsdosedwithTG100-115asasingle0.5mg/kgi.v.bolus30minafterreperfusiondevelopedsmallerinfarctsvs.vehicle-treatedcontrols.MeasuringinfarctareaaspercentoftotalLVischemicarea,infarctsizeisreducedby35%(P=0.04).Viabletissuewithintheischemiczoneisincreasedby37%(P=0.04),directlydemonstratingthecardioprotectiveeffectofPI3Kγ/δinhibition[1].PROTOCOLKinaseAssay[1]PI3Kreactionsareconstructedbyusingrecombinanthumankinases,3μMATP,phosphatidylinositolsubstrate,andcofactors,andreactionprogressionmeasuredbyusingaluminescent-baseddetectionsystemtoquantifyATPconsumption.Proteinkinaseassaysareperformedbyusingcommercialscreeningservices[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]HumanumbilicalveinECplatedin96-wellclusterplates(5,000cells/well)areculturedinassaymedium(containing0.5%serumand50ng/mLVEGF)inthepresenceorabsenceoftestcompounds(e.g.,TG100-115)(10μM),andcellnumbersarequantifiedbyXTTassay24,48,or72hlater[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats[1]Administration[1]Sprague-Dawleyrats(175-200g)aredosedi.v.witheitherTG100-115(1mg/kg)orvehicle,and1-4hlaterEvansbluedyeisadministeredi.v.as500μlofa2%sterilesalinesolution.Immediatelyafterdyeinjection,animalsareinjectedintradermallyoneachshavedflankwith100μLofsaline,VEGF(2μg/mLstock),or2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEhistamine(10μg/mLstock).Thirtyminuteslater,injectionsitesarephotographed.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•Molecules.2020Apr23;25(8):1980.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DoukasJ,etal.Phosphoinositide3-kinasegamma/deltainhibitionlimitsinfarctsizeaftermyocardialischemia/reperfusioninjury.ProcNatlAcadSciUSA.2006Dec26;103(52):