TAS-117-hydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETAS-117hydrochlorideCat.No.:HY-19934A分?式:C??H??ClN?O?分?量:460.96作?靶點:Akt;Apoptosis;Autophagy作?通路:PI3K/Akt/mTOR;Apoptosis;Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:62.5mg/mL(135.59mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1694mL10.8469mL21.6939mL5mM0.4339mL2.1694mL4.3388mL10mM0.2169mL1.0847mL2.1694mL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(fù)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(jié)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:≥2.08mg/mL(4.51mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.51mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.51mM);ClearsolutionBIOLOGICALACTIVITY?物活性TAS-117hydrochloride?種有效、選擇性、具有?服活性的別構(gòu)Akt抑制劑(對Akt1、2和3的IC50分別為4.8、1.6和44nM)。TAS-117hydrochloride激發(fā)抗?髓瘤活性并增強蛋?酶體抑制誘導(dǎo)的致命內(nèi)質(zhì)?應(yīng)激。TAS-117hydrochloride誘導(dǎo)細胞凋亡(apoptosis)和?噬(autophagy)。IC50&TargetAkt1Akt2Akt34.8nM(IC50)1.6nM(IC50)44nM(IC50)體外研究TAS-117(1μM;6hours)blocksbasalphosphorylationofAktanddownstreamp-FKHR/FKHRL1inMMcellswithhighbaselinep-Akt[1].TAS-117(0-10μM;72hours)selectivelyinhibitsAktandinducescytotoxicityinMMcellswithhighbaselinephosphorylationofAkt[1].TAS-117abrogatesthecytoprotectiveeffectofthebonemarrowmicroenvironmentassociatedwithAktinhibitioninbothMMcellsandBMSCs.TAS-117enhancesCarfilzomib-inducedcytotoxicityandfatalERstressinMMcells.TAS-117(0.5,1μM)triggersG0/G1arrestfollowedbyapoptosis,associatedwithinductionofautophagyandendoplasmicreticulumstressresponse[1].TAS-117enhancesbortezomib-inducedcytotoxicity,associatedwithincreasedCHOP(afatalER-stressmarker)andPARPcleavageandblockadeofbortezomib-inducedp-Akt,suggestingthatTAS-117augmentsBortezomib-inducedERstressandapoptoticsignaling[1].CellViabilityAssay[1]CellLine:MMcelllinesConcentration:0-10μMIncubationTime:72hoursResult:InducedsignificantgrowthinhibitioninMMcelllineswithhighbaselinep-Akt,butnotincelllineswithlowbaselinep-Akt.WesternBlotAnalysis[1]CellLine:MM.1S,MM.1R,H929,andKMS11cellsConcentration:1μMIncubationTime:6hoursResult:BlockedbasalphosphorylationofAktanddownstreamp-FKHR/FKHRL1inMMcellswithhighbaselinep-Akt,butdidnotinhibitautophosphorylationofPDK1whichphosphorylatesAktatThr308.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體內(nèi)研究TAS-117(12-16mg/kg;p.o.;dailyfor5daysaweek,21days)inhibitstumorgrowthinmurinexenograftmodelsofhumanMM[1].TAS-117enhancesbortezomib-inducedMMcytotoxicityinvivo[1].AnimalModel:SCIDmice(xenograftmodelsbearingMM.1Scells)[1]Dosage:12,16mg/kgAdministration:P.o.;dailyfor5daysaweek,21daysResult:SignificantlyreducedMM.1Stumorgrowthversusvehiclecontrol.REFERENCES[1].MimuraN,etal.SelectiveandpotentAktinhibitiontriggersanti-myelomaactivitiesandenhancesfatalendoplasmicreticulumstressinducedbyproteasomeinhibition.CancerRes.2014;74(16):4458-4469.McePdfHeightCaution:Producth