Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAS-605240Cat.No.:HY-10109CASNo.:648450-29-7分?式:C??H?N?O?S分?量:257.27作?靶點(diǎn):PI3K;Autophagy作?通路:PI3K/Akt/mTOR;Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:25mg/mL(97.17mM;ultrasonicandadjustpHto10withNaOH)H2O:2.78mg/mL(10.81mM;ultrasonicandwarmingandadjustpHto10withNaOHandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.8870mL19.4348mL38.8697mL5mM0.7774mL3.8870mL7.7739mL10mM0.3887mL1.9435mL3.8870mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：0.5%CMC-Na>>0.5%Tween-801/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:6.25mg/mL(24.29mM);Suspenedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(9.72mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(9.72mM);ClearsolutionBIOLOGICALACTIVITY?物活性AS-605240?種?服有效的特異性PI3Kγ抑制劑，IC50值為8nM，Ki值為7.8nM。IC50&TargetPI3KαPI3KβPI3KδPI3Kγ60nM(IC50)270nM(IC50)300nM(IC50)8nM(IC50)PI3KγAutophagy7.8nM(Ki)體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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