SIAIS178-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESIAIS178Cat.No.:HY-128756CASNo.:2376047-73-1分?式:C??H??ClN??O?S?分?量:1012.68作?靶點(diǎn):PROTACs;Bcr-Abl作?通路:PROTAC;ProteinTyrosineKinase/RTK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:300mg/mL(296.24mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM0.9875mL4.9374mL9.8748mL5mM0.1975mL0.9875mL1.9750mL10mM0.0987mL0.4937mL0.9875mL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%salineSolubility:≥7.5mg/mL(7.41mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性SIAIS178?種PROTAC類的有效的，選擇性的BCR-ABL降解劑，IC50為24nM。SIAIS178通過募集VonHippel-Lindau(VHL)E3泛素連接酶來降解BCR-ABL蛋?。SIAIS178具有抗腫瘤活性。IC50&TargetVHLBcr-Abl24nM(IC50)體外研究SIAIS178(1-100nM;for16hours)significantlyreducestheBCR-ABLproteinlevelsinaconcentrationdependentmanner.SIAIS178significantlyinhibitsthephosphorylationofBCR-ABLandthesubstratesSTAT5[1].SIAIS178(1,10,100,1000nM)exertssignificantantiproliferativeactivityinBCR-ABLdrivenCMLcelllines.SIAIS178retainspotencyandselectivityagainsttheBCR-ABLdrivencelllines[1].WesternBlotAnalysis[1]CellLine:K562cellsConcentration:1,3,10,30,100nMIncubationTime:16hoursResult:SignificantlyreducedtheBCR-ABLproteinlevelsinaconcentrationdependentmanner.體內(nèi)研究SIAIS178(ip;5,15,and45mg/kg;12days)attenuatestumorprogressioninadose-dependentmanner,asdeterminedbyserialvolumetricmeasurement[1].SIAIS178(ivorip;2mg/kg;24hours)hasT1/2of3.82and12.35hoursandCmaxof1165.2nMand30nMforivandip,respectively[1].AnimalModel:NOD/SCIDmicewithtermedK562-Luc[1]Dosage:5,15,and45mg/kgAdministration:Ip;12daysResult:Attenuatedtumorprogressioninadose-dependentmanner,asdeterminedbyserialvolumetricmeasurement.AnimalModel:FemaleWistarrats[1]Dosage:2mg/kg(PharmacokineticAnalysis)Administration:Ivorip;24hoursResult:HadT1/2of3.82and12.35hoursandCmaxof1165.2nMand30nMforivandip,respectively.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].ZhaoQ,etal.DiscoveryofSIAIS178asanEffectiveBCR-ABLDegraderbyRecruitingVonHippel-Lindau(VHL)E3UbiquitinLigase.JMedChem.2019Oct24;62(20):9281-9298.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalap