Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETG100-115Cat.No.:HY-10111CASNo.:677297-51-7分?式:C??H??N?O?分?量:346.34作?靶點:PI3K作?通路:PI3K/Akt/mTOR儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:33.33mg/mL(96.23mM;ultrasonicandwarmingandadjustpHto2withHClandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8873mL14.4367mL28.8734mL5mM0.5775mL2.8873mL5.7747mL10mM0.2887mL1.4437mL2.8873mL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。-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?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：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(7.22mM);Clearsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(7.22mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性TG100-115?種選擇性的PI3Kγ/PI3Kδ抑制劑，IC50分別為83和235nM。IC50&TargetPI3KδPI3Kγ235nM(IC50)83nM(IC50)體外研究TG100-115inhibitsPI3KγandPI3KδwithIC50sof83and235nM,respectively,whereasbothPI3KαandPI3Kβarerelativelyunaffected(IC50values>1μM).Asagaugeofgeneralspecificity,TG100-115isalsoassayedagainsta133proteinkinasepanel,noneofwhichareinhibitedatIC50values[1].體內(nèi)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?邊的抑制劑?師www.MedChemEhistamine(10μg/mLstock).Thirtyminuteslater,injectionsitesarephotographed.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?Molecules.2020Apr23;25(8):1980.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DoukasJ,etal.Phosphoinositide3-kinasegamma/deltainhibitionlimitsinfarctsizeaftermyocardialischemia/reperfusioninjury.ProcNatlAcadSciUSA.2006Dec26;103(52):