KI-ARv-03-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEKI-ARv-03Cat.No.:HY-153718CASNo.:2416873-72-6分子式:C₁₄H₂₁N₅分子量:259.35作用靶点:LigandsforTargetProteinforPROTAC;CDK;c-Myc作用通路:PROTAC;CellCycle/DNADamage;Apoptosis储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 KI-ARv-03是一种强效且选择性的ATP竞争性CDK9抑制剂，IC50为0.15μM(在45μMATP浓度下)，对其他CDK(包括CDK1-7)的选择性超过130倍。KI-ARv-03可降低前列腺癌细胞中AR驱动的转录和增殖。KI-ARv-03可用于白血病、胰腺癌、肺泡横纹肌肉瘤(ARMS)和去势抵抗性前列腺癌(CRPC)的相关研究。KI-ARv-03是PROTAC靶蛋白的配体(ligandfortargetproteinforPROTAC)。KI-ARv-03可用于合成PROTACKI-CDK9d-32(HY-173523)[1][2]。IC50&TargetCDK90.15μM(IC50)体外研究KI-ARv-03bindsintheATP-pocketofCDK9,formingcriticalinteractionswithhingeresiduesGlu107,His108,andtheDFG-motif'sAsp109[1].KI-ARv-03(5μM,18h)selectivelysuppressedAR-V7transcriptsinbothVCaP-16and22Rv1cells,aneffectthattranslatedtoKLK3downregulationonlyinVCaP-16cells,withnoimpactonAR-FL[1].KI-ARv-03(0-10μM,48-72h)exhibitsdose-dependentanti-proliferativeactivity(GR₅₀=1.52μMinMV-4-11;GR₅₀=3.26μMin22Rv1)andinducesmorerobustapoptosisinMV-4-11AMLcells,suggestingaheightenedsusceptibilityofhematologicalcancerstoCDK9inhibition[1].KI-ARv-03(0-40μM,1h)directlyengagesCDK9butnotARspecies,indicatingitaffectsARlevelsthroughimpairedCDK9enzymaticactivity[1].KI-ARv-03(0.5-10μM,1-48h)dose-dependentlyreducesRNAPolII(pSer2/pSer7),andtime-dependentlydepletesAR-FL,AR-V7andAR(pSer81)levelsin22Rv1cells,consistentwithitsroleinCDK9-mediatedtranscriptionalregulationoftheARlocus[1].KI-ARv-03(5μM,6-24h)triggersthedepletionofARproteinthroughaproteasome-dependentpathway,asevidencedbyrescuewithMG132(HY-13259),therebylinkingCDK9inhibitiontoARproteinstability[1].1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEKI-ARv-03(0-10μM,72-120h)dose-dependentlyinhibitstheproliferationofMOLT-4,PSN-1,andRH-4cells,withIC₅₀valuesrangingfrom279.2nMto9.99μM[2].RealTimeqPCR[1]CellLine:VCaP-16and22Rv1cellsConcentration:5μMIncubationTime:18hResult:DramaticallydecreasedtranscriptlevelsofKLK3(PSA)andAR-V7inVCaP-16cells.DecreasedAR-V7transcript,whileKLK3transcriptlevelsshowednosignificantreductionin22Rv1cells.TranscriptlevelsofAR-FLremainedunchangedinbothcelllines.ApoptosisAnalysis[1]CellLine:MV-4-11and22Rv1cellsConcentration:10μMtop,3.16-folddilutionIncubationTime:48hforMV-4-11,and72hfor22Rv1Result:Moderatelyincreasedapoptoticcellcountsathighdoses(10and3μM),whilenoapoptoticcellswereproducedatsubmicromolardoses.CellProliferationAssay[1]CellLine:MV-4-11and22Rv1cellsConcentration:10μMtop,3.16-folddilutionIncubationTime:48hforMV-4-11,and72hfor22Rv1Result:Inhibitedcellproliferationinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:22Rv1cellsConcentration:0.5,2.5,5and10μMIncubationTime:1,2,4,6,8,24,and48hResult:SignificantlyreducedphosphorylationofRNAPolIIatSer2andSer7,evenatlowdoses.SignificantlyreducedAR-FL,AR-V7proteinlevelsandARphosphorylationatSer81startingat6h,withcompletedepletionachievedafter16h.ThedepletionofARproteinwasrescuedbyco-treatmentwiththeproteasomeinhibitorMG132(10μM).2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEREFERENCESRichtersA,etal.ModulatingAndrogenReceptor-DrivenTranscriptioninProstateCancerwithSelectiveCDK9Inhibitors.CellChemBiol.2021Feb18;28(2):134-147.e14ToureMA,etal.TargeteddegradationofCDK9potentlydisruptstheMYC-regulatednetwork.CellChemBiol.2025Apr17;32(4):542-555.e10.McePdfHeightCaution