Theophylline-platinum-IV-prodrug-1-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemETheophylline-platinum(IV)prodrug-1Cat.No.:HY-175257分子式:C₂₅H₄₆Cl₂N₆O₆Pt分子量:792.66作用靶点:PARP;ReactiveOxygenSpecies(ROS);Apoptosis;NF-κB;ERK;Bcl-2Family;TGF-βReceptor;EGFR;Cadherin作用通路:CellCycle/DNADamage;Epigenetics;Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;Apoptosis;MAPK/ERKPathway;StemCell/Wnt;TGF-beta/Smad;JAK/STATSignaling;ProteinTyrosineKinase/RTK;Cytoskeleton储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Theophylline-platinum(IV)prodrug-1是一种PARP-1抑制剂。Theophylline-platinum(IV)prodrug-1可增强SKOV3-BRCA1-KD细胞的DNA损伤、ROS产生、线粒体功能障碍、凋亡(apoptosis)和S期阻滞，同时减少侵袭和转移。Theophylline-platinum(IV)prodrug-1在SKOV3-BRCA1-KD异种移植肿瘤模型中显示出优越的抗肿瘤活性。Theophylline-platinum(IV)prodrug-1可用于卵巢癌的研究[1]。体外研究Theophylline-platinum(IV)prodrug-1(Compound4)(10-10-10-3μM,72h)inhibitstheproliferationofSKOV3cells(IC50=0.13μM),SKOV3-BRCA1-KDcells(IC50=0.1μM),A549cells(IC50=0.31μM),A549-BRCA1-KDcells(IC50=0.18μM),MCF-7cells(IC50=0.10μM),MCF-7-BRCA1-KDcells(IC50=0.04μM),MDA-MB-231cells(IC50=0.08μM),IOSE-80cells(IC50=0.18μM)andSIcells(IC50=18μM)[1].Theophylline-platinum(IV)prodrug-1(10μM,6h)inducesDNAdamageinSKOV3andSKOV3-BRCA1-KDcells[1].Theophylline-platinum(IV)prodrug-1(0.5-2μM,24h)inducesROSproduction,mitochondrialmembranepotentialdamage,cellcyclearrestandapoptosisinSKOV3andSKOV3-BRCA1-KDcells[1].Theophylline-platinum(IV)prodrug-1(0.5μM,24h)inducesinvasionandmetastasisinhibitioninSKOV3andSKOV3-BRCA1-KDcells[1].Immunofluorescence[1]CellLine:SKOV3andSKOV3-BRCA1-KDcellsConcentration:0.5,1,10μM1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEIncubationTime:6,24hResult:Inducedaremarkable15.13-foldincreaseinγH2AXfociformationinSKOV3-BRCA1-KDcells.Showeda4.45-foldincreaseintheolivetailmomentcomparedtoCisplatin(HY-17394)inBRCA1-deficientcells.Resultedinlargerandmoreintensefoci,suggestingamoresevereandpotentiallyirreparableformofDNAdamage.InducedROSeffectsinBRCA1-deficientcellsparticularly.ShowedthemostsignificanteffectonMMPinbothcelllines,withtheeffectbeingmorepronouncedinSKOV3-BRCA1-KDcells.CellCycleAnalysis[1]CellLine:SKOV3andSKOV3-BRCA1-KDcellsConcentration:1μMIncubationTime:24hResult:ResultedinanS-phasecellproportionof38.67%inSKOV3cellsandledtoanS-phasecellproportionof63.52%inBRCA1-deficientcells.ShowedS-phasearrestinBRCA1-deficientcells.ApoptosisAnalysis[1]CellLine:SKOV3andSKOV3-BRCA1-KDcellsConcentration:2μMIncubationTime:24hResult:ShowedparticularlynotableapoptosisinductioneffectsinSKOV3andSKOV3-BRCA1-KDcells.ExhibitedanevenmorestrikingeffectonSKOV3cells,inducingapoptosisin25.7%ofthepopulation.Immunofluorescence[1]CellLine:SKOV3andSKOV3-BRCA1-KDcellsConcentration:1μMIncubationTime:15hResult:DecreasedPARP-1levelsinSKOV3-BRCA1-KDcells.UpregulatedγH2AXlevelsparticularlyinBRCA1-deficientcancercells.2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEEnhancedthepro-apoptoticproteinBaxlevelsandsuppressedtheantiapoptoticproteinBcl-2levels.DownregulatedNF-κB,TGF-β,Smad2,EGFRandE-cadherinlevels.IncreasedtheexpressionofN-cadherinandvimentin.体内研究Theophylline-platinum(IV)prodrug-1(Compound4)(2.5mg/kg,i.v.,everythreedaysforatotalofsixdoses)exhibitssuperiorantitumoractivityinthexenograftSKOV3-BRCA1-KDtumormodel[1].AnimalModel:FemaleBALB/c-nudemiceusingacell-derivedxenograft(CDX)SKOV3-BRCA1-KDtumormodel[1]Dosage:2.5mg/kgAdministration:i.v.everythreedaysforatotalofsixdosesResult:Inhibitedtumorgrowthby71.70%.Maintainedstablebodyweights.Showednosignificantchangesinanyofthesehematologicalparameters.Exhibitedanear-normalmorphology,similartothatofthecontrolgroup.ReducedPARP-1proteinexpression.REFERENCESLiuXM,etal.Precision-OrientedTheophylline-Platinum(IV)Prodrugs:ElicitingSyntheticLethalityinBRCA1-DeficientOvarianCancerwithEnhancedEfficacyandReducedToxicityInVitroandInVivo.JMedChem.2025Jul24;68(14):14995