TAS-117-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETAS-117hydrochlorideCat.No.:HY-19934A分⼦式:C₂₆H₂₅ClN₄O₂分⼦量:460.96作⽤靶点:Akt;Apoptosis;Autophagy作⽤通路:PI3K/Akt/mTOR;Apoptosis;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:62.5mg/mL(135.59mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1694mL10.8469mL21.6939mL5mM0.4339mL2.1694mL4.3388mL10mM0.2169mL1.0847mL2.1694mL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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.51mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.51mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.51mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性TAS-117hydrochloride⼀种有效、选择性、具有⼝服活性的别构Akt抑制剂(对Akt1、2和3的IC50分别为4.8、1.6和44nM)。TAS-117hydrochloride激发抗⾻髓瘤活性并增强蛋⽩酶体抑制诱导的致命内质⽹应激。TAS-117hydrochloride诱导细胞凋亡(apoptosis)和⾃噬(autophagy)。IC50&TargetAkt1Akt2Akt34.8nM(IC50)1.6nM(IC50)44nM(IC50)体外研究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—您⾝边的抑制剂⼤师www.MedChemE体内研究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