Prexasertib-mesylate-LY2606368-mesylate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPrexasertibmesylateCat.No.:HY-18174CCASNo.:1234015-55-4Synonyms:LY2606368mesylate分⼦式:C₁₉H₂₃N₇O₅S分⼦量:461.49作⽤靶点:CheckpointKinase(Chk);DNA/RNASynthesis;Apoptosis作⽤通路:CellCycle/DNADamage;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Prexasertib(LY2606368)mesylate⼀种选择性的，ATP竞争性的第⼆代细胞周期检测点激酶1(CHK1)抑制剂，Ki为0.9nM，IC50为50=8nM)和RSK1(IC50=9nM)。Prexasertibmesylate引起双链DNA断裂和复制突变，导致细胞凋亡(apoptosis)。Prexasertibmesylate显⽰有效的抗肿瘤活性。IC50&TargetChk1Chk1Chk20.9nM(Ki)50)8nM(IC50)体外研究Prexasertib(LY2606368)mesylateinhibitsMELK(IC50=38nM),SIK(IC50=42nM),BRSK2(IC50=48nM),ARK5(IC50=64nM).PrexasertibmesylaterequiresCDC25AandCDK2tocauseDNAdamage[1].Prexasertibmesylate(33,100nM;for7hours)resultsinDNAdamageduringS-phaseinHeLacells[1].Prexasertibmesylate(8-250nM;pre-treatedfor15minutes)inhibitsCHK1autophosphorylation(S296)andCHK2autophosphorylation(S516)inHT-29cells[1].Prexasertibmesylate(4nM;24hours)resultsinalargeshiftincell-cyclepopulationsfromG1andG2-MtoS-phasewithanaccompaniedinductionofH2AXphosphorylationinU-2OScells[1].Prexasertibmesylate(33nM;for12hours)causeschromosomalfragmentationinHeLacells.Prexasertibmesylate(100nM;0.5to9hours)inducesreplicationstressanddepletesthepoolofavailableRPA2forbindingtoDNA[1].CellCycleAnalysis[1]CellLine:HeLacells1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:33,100nMIncubationTime:7hoursResult:HadanIC50of37nMandresultedintheG2-MpopulationreceivedDNAdamageduringS-phasebutcontinuedtoprogressthroughthecellcycleintoanearlymitosis.WesternBlotAnalysis[1]CellLine:HT-29cellsConcentration:8,16,31,63,125,250nMIncubationTime:Pre-treatedfor15minutesResult:InhibitedCHK1autophosphorylation(S296)andCHK2autophosphorylation(S516)(IC50oflessthan31nM)inHT-29cells.体内研究Prexasertibmesylate(1-10mg/kg;SC;twicedailyfor3days,rest4days;forthreecycles)causesgrowthinhibitionintumorxenografts[1].Prexasertibmesylate(15mg/kg;SC)causesCHK1inhibitioninthebloodandthephosphorylationofbothH2AX(S139)andRPA2(S4/S8)[1].AnimalModel:FemaleCD-1nu-/nu-mice(26-28g)withCalu-6cells[1]Dosage:1,3.3,or10mg/kgAdministration:SC;twicedailyfor3days,rest4days;forthreecyclesResult:Causedstatisticallysignificanttumorgrowthinhibition(upto72.3%).户使⽤本产品发表的科研⽂献•NatCommun.2019Aug2;10(1):3485.•BrJCancer.2021Mar26.•Thorax.2021Jul5;thoraxjnl-2021-217377.•Oncogene.2022Oct12.•CellBiolToxicol.2021Sep14.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].KingC,etal.LY2606368CausesReplicationCatastropheandAntitumorEffectsthroughCHK1-DependentMechanisms.MolCancer2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemETher.2015Sep;14(9):2004-1.[2].YinY,etal.Chk1inhibitionpotentiatesthetherapeuticefficacyofPARPinhibitorBMN673ingastriccancer.AmJCancerRes.2017Mar1;7(3):473-483.McePdfHeightCaution:Producthasnotbeenfully