Vps34-PIK-III-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVps34-PIK-IIICat.No.:HY-12794CASNo.:1383716-40-2分?式:C??H??N?分?量:319.36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:≥31mg/mL(97.07mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.1313mL15.6563mL31.3126mL5mM0.6263mL3.1313mL6.2625mL10mM0.3131mL1.5656mL3.1313mL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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(7.83mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.83mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.83mM);ClearsolutionBIOLOGICALACTIVITY?物活性Vps34-PIK-III?種具有?服活性和選擇性的VPS34抑制劑(IC50=18nM)。Vps34-PIK-III能有效抑制?噬，可作為分??具使?。Vps34-PIK-III也?種PI3K抑制劑，能抑制肝臟癌癥?細(xì)胞(CSCs)因的表達(dá)。IC50&TargetVps34PI(3)KδPI(3)KγPI(3)Kα18nM(IC50)1.2μM(IC50)3.04μM(IC50)3.96μM(IC50)體外研究Vps34-PIK-III(1,5,10μM;24h)inhibitsautophagyandLC3lipidationinDLD1cells[1].Vps34-PIK-III(1,5,10μM;24h)leadstoanincreaseinthelipidatedandnonlipidatedformsofLC3inDLD1cells[1].Vps34-PIK-III(5μM;24h)significantlydecreasestheexpressionofstemnessgenesinHCCcells[2].Vps34-PIK-III(5μM;24h)suppressesliverCSCsviaAMPKactivationinHuh7andMHCC97Hcells[2].CellViabilityAssay[1]CellLine:DLD1cellsConcentration:1,5,10μMIncubationTime:24hResult:Preventedthedegradationofautophagysubstratesp62,NCOA4,NBR1,NDP52,andFTH1.RT-PCR[1]CellLine:HCCcellsConcentration:5μMIncubationTime:24hResult:Inhibitedstemnessgenesexpression.WesternBlotAnalysis[1]CellLine:Huh7andMHCC97HcellsConcentration:5μM2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:24hResult:InhibitedliverCSCsbyactivatingAMPK.體內(nèi)研究Vps34-PIK-III(10mg/kg;p.o.;single)rapidlyabsorbedandshowsmoderatemeansystemicclearance(30mL/min/kg,approximately33%ofhepaticbloodflow),withgoodoralbioavailability(F%=47)[1].AnimalModel:C57BL/6mice[1].Dosage:10mg/kg;2mg/kgAdministration:Oraladministration;intravenousinjection;singleResult:1.19PharmacokineticParametersofVps34-PIK-IIIinC57BL/6mice[1].IV(2mg/kg)PO(10mg/kg)Tmax(h)0.7Cmax(nM)2994AUCinf(nM?h)28556725t1/2(h)1.2CL(mL/min/kg)30Vdss(L/kg)1.5F(%)47%戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?FrontCardiovascMed.22September2021.?MolImmunol.2021Feb5.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HondaA,etal.Potent,Selective,andOrallyBioavailableInhibitorsofVPS34ProvideChemicalToolstoModulateAutophagyinVivo.ACSMedChemLett.2015Nov13;7(1):72-6.[2].LiuF,etal.PIK3C3regulatestheexpansionofliverCSCsandPIK3C3inhibitioncounteractslivercancerstemcellactivityinducedbyPI3Kinhibitor.CellDeathDis.2020Jun8;11(6):427.[3].DowdleWE,etal.SelectiveVPS34inhibitorblocksautophagyanduncoversaroleforNCOA4inferritindegradationandironhomeostasisinvivo.NatCellBiol.2014Nov;16(11):1069-79.McePdfHeightCaution:Producth