Casein-Kinase-inhibitor-A86-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECaseinKinaseinhibitorA86Cat.No.:HY-123955CASNo.:2079069-01-3分⼦式:C₁₈H₂₅FN₆分⼦量:344.43作⽤靶点:CaseinKinase;CDK;Apoptosis作⽤通路:CellCycle/DNADamage;StemCell/Wnt;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:12.5mg/mL(36.29mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.9033mL14.5167mL29.0335mL5mM0.5807mL2.9033mL5.8067mL10mM0.2903mL1.4517mL2.9033mL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:≥1.25mg/mL(3.63mM);Clearsolution1/2MasterofBioactiveMolecules—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:≥1.25mg/mL(3.63mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(3.63mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性CaseinKinaseinhibitorA86⼀种有效且具有⼝服活性的酪蛋⽩激酶1α(CK1α)抑制剂。CaseinKinaseinhibitorA86还抑制CDK7(TFIIH)和CDK9(P-TEFb)。CaseinKinaseinhibitorA86可诱导⽩⾎病细胞凋亡(apoptosis)，并具有有效的抗⽩⾎病活性。IC50&TargetCKIαCDK7CDK90.31nM(Kd)5.4nM(Kd)体外研究CaseinKinaseinhibitorA86ishighlyeffectiveininducingleukemiacellapoptosisat160nMorlower,mostlyincorrelationtotheircapacitytostabilizep53[1].CaseinKinaseinhibitorA86(0.08-2μM;6.5hours)abolishestheexpressionofMYC,MDM2,andtheanti-apoptoticoncogeneMCL1.CaseinKinaseinhibitorA86inducesamarkedreductioninmRNAexpressionofMYCandMDM2,yetupregulatestheexpressionoftheWnttargetsAXIN2andCCND1(CyclinD1)[1].CellViabilityAssay[1]CellLine:MV4-11cellsConcentration:0.08μM,0.6μM,2μMIncubationTime:6.5hoursResult:AbolishestheexpressionofMYC,MDM2,andtheanti-apoptoticoncogeneMCL1.体内研究PharmacokineticstudiesoftheinhibitorCaseinKinaseinhibitorA86at20mg/kgrevealrapidoralabsorptionwithaTmaxof0.2-0.5hr,Cmaxof1115ng/mL,T1/2of4.3hr,andareaunderthecurve(AUC)valuesof2606(ng*hr/mL)[1].REFERENCES[1].WaleedMinzel,etal.SmallMoleculesCo-targetingCKIαandtheTranscriptionalKinasesCDK7/9ControlAMLinPreclinicalModels.Cell.2018Sep20;175(1):171-185.e25.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplication