Casein-Kinase-inhibitor-A51-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECaseinKinaseinhibitorA51Cat.No.:HY-123954CASNo.:2079068-74-7分?式:C??H??ClN?分?量:360.88作?靶點(diǎn):CaseinKinase;CDK;Apoptosis作?通路:CellCycle/DNADamage;StemCell/Wnt;Apoptosis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:100mg/mL(277.10mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.7710mL13.8550mL27.7100mL5mM0.5542mL2.7710mL5.5420mL10mM0.2771mL1.3855mL2.7710mL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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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:≥2.5mg/mL(6.93mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.93mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.93mM);ClearsolutionBIOLOGICALACTIVITY?物活性CaseinKinaseinhibitorA51?種有效且具有?服活性的酪蛋?激酶1α(CK1α)抑制劑。CaseinKinaseinhibitorA51可誘導(dǎo)??病細(xì)胞凋亡(apoptosis)，并具有有效的抗??病活性。IC50&TargetCKIαCDK7CDK91.3nM(Kd)4nM(Kd)體外研究SimilartoCKIαdepletion,CaseinKinaseinhibitorA51(0.05-3.2μM;18hours)treatmentofRKOcellsabolishedmostoftheSer45phosphorylationsignalandtheconsecutiveGSK3phosphorylationcascaderesultinginstabilizationofβ-catenin[1].CaseinKinaseinhibitorA51ishighlyeffectiveininducingleukemiacellapoptosisat160nMorlower,mostlyincorrelationtotheircapacitytostabilizep53[1].CaseinKinaseinhibitorA51(0.08-2μM;6.5hours)abolishestheexpressionofMYC,MDM2,andtheanti-apoptoticoncogeneMCL1.CaseinKinaseinhibitorA51inducesamarkedreductioninmRNAexpressionofMYCandMDM2,yetupregulatestheexpressionoftheWnttargetsAXIN2andCCND1(CyclinD1)[1].CellViabilityAssay[1]CellLine:MV4-11cellsConcentration:0.08μM,0.6μM,2μMIncubationTime:6.5hoursResult:AbolishestheexpressionofMYC,MDM2,andtheanti-apoptoticoncogeneMCL1.體內(nèi)研究Oraltreatmentisinitiatedat8days(CaseinKinaseinhibitorA51;5mg/kg/day)afterleukemiacellinoculation,atwhichthepercentageofleukemiacellsintheBMismorethan1.5%ofallcells.allA51-treatedmicehavenormalorganmorphologyandhistologyandnormalbloodcounts[1].PharmacokineticstudiesoftheinhibitorCaseinKinaseinhibitorA51at20mg/kgrevealrapidoralabsorptionwithaTmaxof0.5-2hr,Cmaxof1060ng/mL,T1/2of2.5hr,andareaunderthecurve(AUC)valuesof3680(ng*hr/mL)[1].REFERENCES[1].WaleedMinzel,etal.SmallMoleculesCo-targetingCKIαandtheTranscriptionalKinasesCDK7/9ControlAMLinPreclinicalModels.Cell.2018Sep20;175(1):171-185.e25.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalidate