Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETAS0728Cat.No.:HY-111553CASNo.:2088323-16-2分?式:C??H??N?O?分?量:504.58作?靶點:EGFR作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(247.73mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.9818mL9.9092mL19.8185mL5mM0.3964mL1.9818mL3.9637mL10mM0.1982mL0.9909mL1.9818mL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(4.12mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.12mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.12mM);ClearsolutionBIOLOGICALACTIVITY?物活性TAS0728?種有效的、選擇性的、?服活性的、不可逆的共價結(jié)合HER2抑制劑，其IC50為13nM。TAS0728對于BMX、HER4、BLK、EGFR、JAK3、SLK和LOK也存在抑制效果，其IC50值分別為4.9、8.5、31、65、33、25和86nM。此外，TAS0728對HER2、HER3和下游效應(yīng)蛋?的磷酸化還表現(xiàn)出強??持久的抑制作?。IC50&TargetHER4HER2EGFRBMX8.5nM(IC50)13nM(IC50)65nM(IC50)4.9nM(IC50)BLKJAK3SLKLOK31nM(IC50)33nM(IC50)25nM(IC50)86nM(IC50)體外研究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.體內(nèi)研究TAS0728revealsthesustainedandtargetedinhibitionofphosphorylationofHER2,HER3,AKTandERK.TAS0728alsoshowstheabilityoftumorregressionandlowtoxicity[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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