AS-605240-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAS-605240Cat.No.:HY-10109CASNo.:648450-29-7分⼦式:C₁₂H₇N₃O₂S分⼦量:257.27作⽤靶点:PI3K;Autophagy作⽤通路:PI3K/Akt/mTOR;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:25mg/mL(97.17mM;ultrasonicandadjustpHto10withNaOH)H2O:2.78mg/mL(10.81mM;ultrasonicandwarmingandadjustpHto10withNaOHandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.8870mL19.4348mL38.8697mL5mM0.7774mL3.8870mL7.7739mL10mM0.3887mL1.9435mL3.8870mL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：0.5%CMC-Na>>0.5%Tween-801/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:6.25mg/mL(24.29mM);Suspenedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(9.72mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(9.72mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AS-605240⼀种⼝服有效的特异性PI3Kγ抑制剂，IC50值为8nM，Ki值为7.8nM。IC50&TargetPI3KαPI3KβPI3KδPI3Kγ60nM(IC50)270nM(IC50)300nM(IC50)8nM(IC50)PI3KγAutophagy7.8nM(Ki)体外研究AS-605240isanisoform-selectiveinhibitorofPI3Kγwithover30-foldselectivityforPI3Kδandβ,and18-and7.5-foldselectivityoverPI3Kα,respectively.AS-605240showsaninhibitoryeffectonC5a-mediatedPKBphosphorylationinRAW264mousemacrophageswithanIC50of0.09μM.AS-605240blocksPKBphosphorylationinducedbyMCP-1andhaslittleornoeffectafterstimulationwithCSF-1.AS-605240inhibitsMCP-1-mediatedphosphorylationofPKBanditsdownstreamsubstratesGSK3αandβinaconcentration-dependentmanner.AS605240suppressesinadose-dependentmannertheproliferationofBDC2.5CD4+Tcells[2].体内研究AS-605240(30mg/kgBW,peros,every12h)markedlydecreasesFoxM1expressioninmouselungsandfailstorestorevascularintegrity[1].AS-605240reducesRANTES-inducedperitonealneutrophilrecruitment,withED50of9.1mg/kg.IntheCCL5model,AS-605240showsanED50valueof10mg/kg,incorrelationwiththepercentageofreductionofneutrophilrecruitmentobservedinPik3cg-/-mice.AS-605240(50mg/kg,p.o.)substantiallyreducesclinicalandhistologicalsignsofjointinflammationtoasimilarextenttothatofPik3cg-/-mice[2].AS605240(30mg/kg,i.p.)suppressesintracellularPAktinsplenocytesofNODmiceanddelaysdiabetesonset.AS605240alsopreventsautoimmunediabetesinprediabeticNODmice,andsuppressesautoreactiveTcellswhileincreasingTregsinNODmice.AS605240(30mg/kg,i.p.)reverseshyperglycemiainnewlyhyperglycemicNODmice,reverseshyperglycemiainearlydiabeticNODmicethroughTregsandsuppressesT-cellinfiltrationinpancreaticisletswhileincreasingTregs[3].AS605240(25,50mg/kg)markedlyreducestotalcellcountandnumbersofmacrophages,neutrophilsandlymphocytesinrats.AS605240significantlyreducesthelevelsofTNF-αandIL-1βinBALFto132.7±11.2pg/mLand49.2±11.3pg/mLin25mg/kgAS605240+BLMgroupand131.3±10.7and49.6±8.8pg/mLin50mg/kgAS605240+BLMgroup,respectively.AS605240inhibitsprefibroticcytokinesproductioninbleomycin-inducedpulmonaryfibrosis.AS605240inhibitsphosphorylationofAktofinflammatorycellsinbleomycin-inducedpulmonaryfibrosismodel[4].PROTOCOL2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEKinaseAssay[2]HumanPI3Kγ(100ng)isincubatedatRTwithkinasebuffer(10mMMgCl2,1mMβ-glycerophosphate,1mMDTT,0.1mMNa3VO4,0.1%NaCholateand15MATP/100nCiγ[33P]ATP,finalconcentrations)andlipidvesiclescontaining18MPtdInsand250MofPtdSer(finalconcentrations),inthepresenceofinhibitorsorDMSO.Kinasereactionisstoppedbyadding250gofNeomycin-coatedScintillationProximityAssay(SPA)beadandproceeded.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[3]Atotalof5×105BDC2.5splenocytesand50μg/mLBDC2.5-peptideareincubatedinvitroina96-wellround-bottomplatefor48h.Thentheculturesarepulsedwith1μCioftritiatedthymidine[3H]todeterminecellproliferation.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalInthisstudy,ratsarebredforoneweektoaffirmbodyweightandthenrandomLydividedintofourAdministration[4]experimentalgroups:(a)controlgroup(ratsaregivenvehicleonly);(b)BLMgroup(ratsareinducedwithBLM);(c)BLM+25mg/kgAS605240group(ratsareinducedwithBLMandthenadministratedwith25mg/kgAS605240);(d)BLM+50mg/kgAS605240group(thesameprotocolastheformergroupexceptadifferentdoseof50mg/kgAS605240).Inaddition,fiveratsaregiven50mg/kgAS605240onlytodetectwhetherAS605240hasanysideeffectsimultaneouslyasthepreviousfourgroups.Ratsin(c),(d)andAS605240-given-onlygroupareadministeredorally25,50and50mg/kgAS605240bygavagewhileratsincontrolgroupandBLMgrouparegivenonlyequivalentsalineatday-1(thedayratsaregivenBLMismarkedasday-0).Thesamedosageismaintainedonceeverydayfor28days.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellSyst.2020Jan22;10(1):66-81.e11.•CellSyst.2020Jan22;10(1):66-81.e11.•JNeurochem.2022Jun;161(6):478-491.•Molecules.2020Apr23;25(8):1980.•HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].HuangX,etal.Endothelialp110γPI3KMediatesEndothelialRegenerationandVascularRepairAfterInflammatoryVascularInjury.Circulation.2016Mar15;133(11):1093-103.[2].CampsM,etal.BlockadeofPI3Kgammasuppressesjointinflammationanddamageinmousemodelsofrheumat