Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEUlecaciclibCat.No.:HY-147409CASNo.:2075750-05-7分?式:C??H??FN?S分?量:496.65作?靶點:CDK作?通路:CellCycle/DNADamage儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Ulecaciclib?種具有?服活性的細胞周期蛋?依賴激酶(CDK)抑制劑，對CDKs的ki為0.62μM(CDK2/CyclinA)、0.2nM(CDK4/CyclinD1)、3nM(CDK6/CyclinD3)和0.63μM(CDK7/CyclinH)。Ulecaciclib能夠通過?腦屏障，具有良好的藥代動?學特性。IC50&Targetcdk2/cyclinACdk4/cyclinD1cdk6/cyclinD3cdk7-cyclinH0.62μM(Ki)0.2nM(Ki)3nM(Ki)0.63μM(Ki)體外研究Ulecaciclib(compound2)(40min)displaysinhibitoryeffectonCDKkinasewithKivaluesof0.62μM(CDK2/A),0.2nM(CDK4/CyclinD1),3nM(CDK6/CyclinD3),0.63μM(CDK7/H),respectively[2].Ulecaciclib(72h)exhibitsastrongantiproliferativeactivityagainstleukemiacellswithagrowthinhibitionGI50valueof10nM[2].Ulecaciclib(72h)inhibitstumorgrowthwithGI50srangefrom0.04-5.09μMandinhibitsOvarianA2780withanGI50valueof40nM,inparticularly[2].CellViabilityAssay[2]CellLine:U87,U251,T98G(mycoplasma-free);andMB453,Colo205,H460,A2780,PANC1,LNC,M229Concentration:0-10μMIncubationTime:72hoursResult:InhibitedcancercellsgrowthwithGI50sof2.17μM(U87),5.09μM(U251),4.18μM1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE(T98G),0.62μM(MB453),1.55μM(Colo205),0.41μM(H460),0.04μM(A2780),1.21μM(PANC1),0.28μM(LNC),0.83μM(M229).體內(nèi)研究Ulecaciclib(compound2)(2mg/kgfori.v.;10mg/kgforp.o.)demonstratesasignificantlypropensitytocrossthebloodbrainbarrierinmice,withthebrain/plasmaratiosare>1.2(i.v.)or>0.7(p.o.),respectively[2].Ulecaciclib(200mg/kg;p.o.;daily;21d)displaysinvivoanti-tumourefficacyinmice[2].Ulecaciclib(25mg/kg;p.o.;daily;10d)demonstratessignificantanti-tumourefficacyatlowerdosesincombinationwithTMZ(5mg/kg;p.o.;5d/week;2weeks)inmice[2].Ulecaciclib(compoundA)(50mg/kg;p.o.)showsanoralbioavailabilityofabout21.8%,andgoodpharmacokineticprofilewithTmaxof6.67handanhalf-of8.34h,whileCmax=643ng/mL,AUC(0-24)=9543ng?h/mLinmalecynomolgusmonkeys[3].PharmacokineticofUlecaciclibincynomolgusmonkeys[3]RouteDose(mg/kg)T1/2(h)Tmax(h)Cmax(ng/mL)AUC(0-t)(h?ng/mL)AUC(0-∞)(h?ng/mL)Vd(L/kg)CL(mL/min/kg)MRT(0-t)(h)F(%)i.v.56.53/447418745609.7919.46.64/p.o.508.346.6764395437305//10.421.8AnimalModel:CDlnu/nufemalemice(5-6weeksold;injectedwithU87GBMcells,s.c.)[2]Dosage:200mg/kgAdministration:Oralgavage;daily;21daysResult:Reducedtumourgrowthmarkedlywithoutanyoverttoxicity.AnimalModel:GBMorthotopicmousexenograftmodels[2]Dosage:120mg/kgAdministration:Oralgavage;dailyfor2daysResult:Inhibitedtumorgrowthonday21andincreasedlifespanratio(ILS)of154.8%forteatedmice.ILS=(DaysT-DaysC)/DaysC,whereDaysC=dayssurvivedbycontrolgroupandDaysT=dayssurvivedbytreatmentgroup.REFERENCES[1].InternationalNonproprietaryNamesforPharmaceuticalSubstances(INN).WHODrugInformation.2022.36(2):337.[2].WangShudong,etal.TreatmentofproliferativediseasesoftheCNSusingaclassofthiazole-pyrimidinecompoundsthatinhibittheactivityofCDK4and/orCDK6[P].WorldIntellectualPropertyOrganization,WO2021222967A12021-11-11.[3].WangShudong,etal.Succinateandcrystalformthereofastherapeutics[P].WorldIntellectualPropertyOrganization,WO2022099357A12022-05-19.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Product