Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOTS964Cat.No.:HY-19718CASNo.:1338542-14-5分?式:C??H??N?O?S分?量:392.51作?靶點(diǎn):TOPK;CDK;Apoptosis作?通路:CellCycle/DNADamage;Apoptosis儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性O(shè)TS964?種?服有效的，?親和?和選擇性的TOPK抑制劑，IC50為28nM。OTS964也?種有效的細(xì)胞周期蛋?依賴激酶CDK11抑制劑，結(jié)合CDK11B的Kd值為40nM。IC50&TargetCDK11BTOPK40nM(Kd)28nM(IC50)體外研究OTS964(10nM;48hours)suppressescancercellproliferation[1].OTS964(10nM;48hours)increasescancercelldeath[1].OTS964(0.1-2μM;24and48hours)increasestheexpressionofLC3-IIanddecreasestheexpressionofP62,bothinadose-dependentmanner[3].CellProliferationAssay[1]CellLine:LU-99cellsConcentration:10nMIncubationTime:48hoursResult:Suppressedcancercellproliferation.ApoptosisAnalysis[1]CellLine:LU-99cells1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:10nMIncubationTime:48hoursResult:Increasedcancercelldeath.WesternBlotAnalysis[3]CellLine:Hs683cells,H4cellsConcentration:0.1,1,2μMIncubationTime:24and48hoursResult:IncreasedtheexpressionofLC3-IIanddecreasedtheexpressionofP62,bothinadose-dependentmanner.體內(nèi)研究OTS964(intravenously;40mg/kgondays1,4,8,11,15,and18)makestumorsshrinkingevenafterthetreatmentandfinallyrevealingcompleteregression[1].OTS964(oraladministration;50or100mg/kg/dayfor2weeks)achievescompletetumorregression[1].AnimalModel:NudemicebearingLU-99lungcancercells[1]Dosage:40mg/kgAdministration:Intravenously;ondays1,4,8,11,15,and18Result:Thetumorscontinuedshrinkingevenafterthetreatmentandfinallyrevealedcompleteregression.AnimalModel:NudemicebearingLU-99lungcancercells[1]Dosage:50or100mg/kgAdministration:Oraladministration;onceeverydayfor2weeksResult:Achievedcompletetumorregression.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Nature.2022Sep;609(7928):829-834.?Cell.2021Jun10;184(12):3143-3162.e32.?CellDeathDis.2019Aug5;10(8):583.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].MatsuoY,etal.TOPKinhibitorinducescompletetumorregressioninxenograftmodelsofhumancancerthroughinhibitionofcytokinesis.SciTranslMed.2014Oct22;6(259):259ra145.[2].LinA,etal.Off-targettoxicityisacommonmechanismofactionofcancerdrugsundergoingclinicaltrials.SciTranslMed.2019Sep11;11(509).[3].LuH,etal.TOPKinhibitsautophagybyphosphorylatingULK1andpromotesgliomaresistancetoTMZ.CellDeathDis.2019Aug5;10(8):583.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappl