Voruciclib-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEVoruciclibhydrochlorideCat.No.:HY-12422ACASNo.:1000023-05-1分⼦式:C₂₂H₂₀Cl₂F₃NO₅分⼦量:506.3作⽤靶点:CDK作⽤通路:CellCycle/DNADamage储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:≥250mg/mL(493.78mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9751mL9.8756mL19.7511mL5mM0.3950mL1.9751mL3.9502mL10mM0.1975mL0.9876mL1.9751mL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(sealedstorage,awayfrommoisture)。-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(4.11mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(4.11mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.11mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Voruciclibhydrochloride⼀种具有⼝服活性和选择性CDK抑制剂，Ki为0.626nM-9.1nM。Voruciclibhydrochloride可以有效阻断MCL-1的转录调节⼦CDK9。Voruciclibhydrochloride抑制多种弥漫性⼤B细胞淋巴瘤(DLBCL)模型中MCL-1的表达。IC50&TargetCDK9/CycT1CDK9/cycT2CDK6/cycD1CDK4/CycD11.68nM(Ki)0.626nM(Ki)2.92nM(Ki)3.96nM(Ki)CDK1/cycBCDK1/cycA5.4nM(Ki)9.1nM(Ki)体外研究Voruciclibhydrochloride(0.5-5µM;6hours)showstargeteddownregulationofMCL-1inbothABCandGCBsubtypes[1].KivaluesforeachtargetsuchasCDK9/cycT2,CDK9/cycT1,CDK6/cycD1,CDK4/cycD1,CDK1/cycB,andCDK1/cycAforVoruciclibhydrochlorideare0.626nM,1.68nM,2.92nM,3.96nM,5.4nM,9.1nM,respectively[1].WesternBlotAnalysis[1]CellLine:U2932,RIVA,OCI-LY10cells(ABCsubtype),NU-DHL-1,SU-DHL-4,SU-DHL-6cells(GCBsubtype)Concentration:0.5µM,1µM,2µM,3µM,4µM,5µMIncubationTime:6hoursResult:ShowedtargeteddownregulationofMCL-1inbothABCandGCBsubtypes.体内研究CombinationofVoruciclibhydrochloride(200mpk;Oralgavage)andVenetoclax(10mpk,1mpk,50mpk,25mpkinU2932,RIVA,SU-DHL-4andNU-DHL-1,respectively)leadstoenhancetumorgrowthinhibitioncomparedtoeitherdrugaloneinU2932,RIVA,SU-DHL-4(sixdaysperweekfor4weeks),andNU-DHL-1models(fivedaysperweekfor3weeks)ofDLBCL[1].AnimalModel:ABCsubtypes(U2932,RIVA,OCI-LY10),GCBsubtypes(SU-DHL-4,NU-DHL-1)xenograftedinFemaleNOD.CB17-Prkdcscid/NCrHsdmice[1]Dosage:200mpkAdministration:Oralgavage;U2932,RIVA,SU-DHL-4(sixdaysperweekfor4weeks),OCI-LY10(six2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEdaysperweekfor2weeks),NU-DHL-1(fivedaysperweekfor3weeks)Result:EnhancedtumorgrowthinhibitioninU2932,RIVA,SU-DHL-4andNU-DHL-1modelsexceptinOCI-LY10model.REFERENCES[1].DeyJ,etal.Voruciclib,aclinicalstageoralCDK9inhibitor,repressesMCL-1andsensitizeshigh-riskDiffuseLargeB-cellLymphomatoBCL2inhibition.SciRep.2017Dec21;7(1):18007.McePdfHeightCaution:Producthasnotbeenful