Sino-C-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESino-CCat.No.:HY-179526分⼦式:C₂₅H₂₅Cl₂NO₄S分⼦量:506.44作⽤靶点:Apoptosis;PARP作⽤通路:Apoptosis;CellCycle/DNADamage;Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Sino-C⼀种具有抗癌活性的Sinomenine(HY-15122)衍⽣物。Sino-C通过上调SREBF2和HMGCS1等关键因⼴泛破坏胆醇稳态，导致细胞内胆醇积聚和脂滴形成。Sino-C诱导的代谢紊乱进⼀步触发脂质过氧化和内质⽹(ER)应激，从⽽启动⼀种独特的混合型细胞死亡形式，包括凋亡(apoptotic)(剪切PARP)及坏死样特征。Sino-C可⽤于结直肠癌、肺癌、乳腺癌研究[1]体外研究Sino-C(0-20μM,48h)exhibitsbroad-spectrumanticanceractivityinCRC(HCT116,RKO,andMC38),lungcancer(A549andNCI-H1299),andbreastcancer(MDA-MB-231and4T1)cells[1].Sino-C(0-20μM,24h)exhibitssignificantanti-CRCeffectinHCT116andRKOcells[1].Sino-C(0-20μM,24h)inducesHCT116andRKOcelldeath,characterizedbyPARPcleavagewithoutcaspase-3activation,causesseveremorphologicalalterations(widenedperinuclearspaces,extensiveERdilationwithribosomedetachment,mitochondrialswelling)alongwithsignificantLDHleakageandmembraneinjury,suggestinganon-apoptoticmechanism[1].Sino-C(24h)elicitsauniqueformofcelldeath:themorphologicalfeaturesdonotmatchthoseofclassicalapoptosis,paraptosis,pyroptosis,orferroptosis,butinsteadrepresentahybridmodecombiningbothapoptoticandnecrotic-likecharacteristicsinHCT116cells[1].Sino-C(0-20μM,24h)upregulatescholesterolhomeostasis-relatedgenes,elevatesintracellularcholesterollevels,andinduceslipiddropletaccumulationinHCT116cells[1].Sino-C(0-20μM,24h)inducescholesteroldysregulation,whichleadstolipidperoxidationandsubsequentlytriggersendoplasmicreticulum(ER)stress,ultimatelycontributingtoCRCcelldeath[1].CellViabilityAssay[1]CellLine:HCT116,RKO,MC38,A549,NCI-H1299,MDA-MB-231,4T11/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:1.25,2.5,5,10and20μMIncubationTime:48hResult:Significantlyreducedcellviabilityinalltestedcelllinesinadose-dependentmanner,withIC50valuespredominantlybelow10μM.ShowedgreaterpotencyagainstCRCcelllines,withIC50valuesof5.15μM(HCT116),9.72μM(RKO),and4.58μM(MC38).CellProliferationAssay[1]CellLine:HCT116andRKOcellsConcentration:0,5,10and20μMIncubationTime:24hResult:RemarkablyinhibitedthecolonyformationofHCT116andRKOcells.ApoptosisAnalysis[1]CellLine:HCT116andRKOcellsConcentration:0,5,10and20μMIncubationTime:24hResult:Revealedadose-dependentincreaseinapoptosis:from5.81%(control)to26.80%(20μM)inHCT116cellsfrom5.39%to22.34%inRKOcells.HadminimalAnnexinV+staininginbothcelllines,indicatingalimitedexternalizationofphosphatidylserineontheplasmamembrane.IncreasedinPI+stainedcellsuponSino-Ctreatment,suggestingthatapoptosismaynotbetheonlycelldeathmode.RT-PCR[1]CellLine:HCT116cellsConcentration:10μMIncubationTime:24hResult:Upregulatedkeygenesinvolvedincholesterolhomeostasis,includingthemastertranscriptionalRegulatorofcholesterolbiosynthesis,SREBF2,aswellasrate-limitingenzymesandakeyReceptorinthepathway,suchasHMGCS1,SQLE,andLDLR.Immunofluorescence[1]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:HCT116cellsConcentration:5,10and20μMIncubationTime:24hResult:Markedlyelevatedintracellularcholesterollevels.体内研究Sino-C(30and50mg/kg,i.t.,everyotherdayfromday14today28)exhibitssignificantanti-CRCeffectinHCT116cellsinduce-BALB/cnudemice[1].AnimalModel:HCT116cells(1×106,s.c.)induce-BALB/cnudemice[1]Dosage:30and50mg/kgAdministration:i.t.,everyotherdayfromday14today22(30mg/kg)theni.t.,everyotherdayfromday24today28(50mg/kg)Result:Significantlyreducedtumorsizeandaveragetumorweightbyapproximately43.24%.Suppressedtumorgrowthoverthetwo-weekstudyperiod.Causednosignificantchangesinmousebodyweight,indicatingminimalsystemictoxicity.REFERENCES[1].ZhangYM,etal.Sino-C,anovelsinomeninederivative,inducescelldeathbyanovelsinomeninederivative,inducescelldeathbydisruptingcholesterolhomeostasisincolorectalcancercells.ActaPharmacolSin.2025Nov3.doi:10.1038/s41401-025-01683-8.Epubaheadofprint.PMID: