TAS0728-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETAS0728Cat.No.:HY-111553CASNo.:2088323-16-2分⼦式:C₂₆H₃₂N₈O₃分⼦量:504.58作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(247.73mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9818mL9.9092mL19.8185mL5mM0.3964mL1.9818mL3.9637mL10mM0.1982mL0.9909mL1.9818mL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(4.12mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.12mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.12mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性TAS0728⼀种有效的、选择性的、⼝服活性的、不可逆的共价结合HER2抑制剂，其IC50为13nM。TAS0728对于BMX、HER4、BLK、EGFR、JAK3、SLK和LOK也存在抑制效果，其IC50值分别为4.9、8.5、31、65、33、25和86nM。此外，TAS0728对HER2、HER3和下游效应蛋⽩的磷酸化还表现出强⼤⽽持久的抑制作⽤。IC50&TargetHER4HER2EGFRBMX8.5nM(IC50)13nM(IC50)65nM(IC50)4.9nM(IC50)BLKJAK3SLKLOK31nM(IC50)33nM(IC50)25nM(IC50)86nM(IC50)体外研究TAS0728isacovalent-bindinginhibitorofHER2kinaseandexhibitshighselectivityforHER2kinase.ItalsoshowsinhibitoryactivityagainstBMX,HER4,BLK,EGFR,JAK3,SLK,andLOK[1].CellCytotoxicityAssay[1]CellLine:HER2-amplifiedSK-BR-3/AU565/BT-474/NCI-N87/Calu-3cellsConcentration:IncubationTime:Result:TheGI50valuesofTAS0728were5.0/5.1/3.6/1.6/6.9nMrelativelyforHER2-amplifiedSK-BR-3/AU565/BT-474/NCI-N87/Calu-3cells.InhibitedtheinvitroproliferationoffiveHER2-amplifiedcelllines.ShowedpotentinhibitoryactivitiesagainstcancercelllineswithHER2amplification.WesternBlotAnalysis[1]CellLine:SK-BR-3cellsConcentration:30-300nMIncubationTime:3and48hoursResult:ShowedsustainedinhibitionofHER2,HER3,AKTandERKphosphorylation.体内研究TAS0728revealsthesustainedandtargetedinhibitionofphosphorylationofHER2,HER3,AKTandERK.TAS0728alsoshowstheabilityoftumorregressionandlowtoxicity[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:MalenudemiceDosage:7.5,15,30and60mg/kgAdministration:Oralgavage;7.5,15,30and60mg/kgaday;14daysResult:Rapidlyeliminatedwithin24hours.AnimalModel:MicebearingNCI-N87xenograftsDosage:60mg/kgAdministration:Oralgavage;60mg/kgaday;14daysResult:RevealedsustainedtargetinhibitionofHER2,HER3,AKTandERK.AnimalModel:MicewithNCI-N87HER2–amplifiedhumangastriccancerDosage:7.5,15,30and60mg/kgAdministration:Oralgavage;7.5,15,30and60mg/kgaday;14daysResult:Welltoleratedinallmice.Significanttumorregressionwasobservedinmicetreatedwith60mg/kg/day.AnimalModel:NCI-N87peritonealdisseminationmodelDosage:30and60mg/kgAdministration:Oralgavage;30and60mg/kgaday;120daysResult:Noevidenttoxicity,includingdiarrheaandbodyweightlossinthelong-termdosingofTAS0728.REFERENCES[1].IrieH,etal.TAS0728,ACovalent-binding,HER2-selectiveKinaseInhibitorShowsPotentAntitumorActivityinPreclinicalModels.Molecularcancertherapeutics.2019;18(4):733-42.Epub2019/02/23.McePdfHeightCaution:Produc