YCH1899-DataSheet-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEYCH1899Cat.No.:HY-155993分子式: C??H??BrFN?O?分子量: 549.35作用靶點(diǎn): PARP作用通路: CellCycle/DNADamage;Epigenetics儲(chǔ)存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性YCH1899是一種具有口服活性的PARP抑制劑，對PARP1/2的IC50均小于0.001nM。YCH1899對Olaparib(HY-10162)耐藥和Talazoparib(HY-16106)耐藥的Capan-1細(xì)胞(Capan-1/OP和Capan-1/TP細(xì)胞)顯示出明顯的抗增殖活性，IC50值分別為0.89和1.13nM。YCH1899在大鼠體內(nèi)具有良好的藥代動(dòng)力學(xué)特性[1]。IC50&TargetPARP-1PARP-2PARP3PARP450)50)1.1nM(IC50)1.0nM(IC50)TNKS1TNKS2PARA6PARP-73.8nM(EC50)12.4nM(IC50)9.5nM(IC50)7.3nM(IC50)ARTD10/PARP10PARA11humanPARP12PARP1410.8nM(IC50)2.166μM(IC50)14.1nM(IC50)35.914μM(IC50)PARP1551.623nM(IC50)體外研究YCH1899(7days)showsobviousanti-proliferationactivityonCapan-1,Capan-1/OPandCapan-1/TPcells,withIC50of0.10,0.89and1.13nM,respectively.[1].YCH1899(0.001-1μM,4h)stabilizesPARP1-DNAcomplexesandsuppressesPARPformation[1].YCH1899(3.5h)inhibitstheproliferationofBRCAmutant/wild-typecells(V-C8,V79,HCT-15,HCC1937)withIC50srangingfrom1.19-44.24nM[1].YCH1899(1μM,24h)causesalargeincreaseinthenumberofγH2AXfociinCapan-1、Capan-1/OP、Capan-1/TPcells[1].YCH1899(1μM,48h)inducesadramaticdecreaseinHR(HomologousRecombination)repairactivityin1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEU2OS-DR-GFPcells[1].CellProliferationAssay[1]CellLine:HCC1937,HCT-15,MDA-MB-436,UWB1.289,UWB1.289+BRCA1,V–C8,V79cellsConcentration:0-1μMapproximatelyIncubationTime:24hResult:InhibitedtheproliferationofBRCA-Deficient/Wild-TypeCellsandIC50svaluewere4.54,44.24,0.52,0.02,0.34,1.19,29.32nM,respectively.Immunofluorescence[1]CellLine:Capan-1,Capan-1/OPcells,Capan-1/TPcellsConcentration:0.01,0.1,1μMIncubationTime:24hResult:IncreasedγH2AXlevelinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:Capan-1andCapan-1/OPcellsConcentration:1,10,100nMIncubationTime:4hResult:ImprovedstabilityofPARP1-DNAcomplexesandinducedchromatin-boundPARP1accumulationinthepresenceofMMS(methanesulfonate).InhibitedPARPformationinthepresenceof0.1%H2O2.體內(nèi)研究YCH1899(5mg/kg,intravenousinjection)hasamoderateclearancerateinrats[1].YCH1899overcomesacquiredTalazoparibresistanceandhasasignificantregressionoftumorvolumeinMDA-MB-436/OP(6.25,12.5,and25mg/kg,orally,onceadayfor27days)andCapan-1/R-invivoxenografts(12.5and25mg/kg,orally,onceadayfor21days)[1].AnimalModel:MDA-MB-436/OPxenograftsandCapan-1/R-invivoxenograftsmice[1]Dosage:12.5and25mg/kgAdministration:OraladministrationResult:InhibitedMDA-MB-436/OPxenograftstumorgrowthwithT/Cof36.74%and15.29%at12.5and25mg/kgInhibitedCapan-1/RxenograftstumorgrowthwithT/Cof48.92%and13.87%at12.52/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEand25mg/kg.AnimalModel:rats[1]Dosage:5mg/kgAdministration:IntravenousinjectionResult:Hadamoderateclearancerate(24.5mL/min/kg)andhalf-life(3.25h).REFERENCESSunY,etal.YCH1899,aHighlyEffectivePhthalazin-1(2H)-oneDerivativeThatOvercomesResistancetoPriorPARPInhibitors.JMedChem.2023Aug21.McePdfHeightCaution:Producthasnotbeenfull