Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESpiclomazinehydrochlorideCat.No.:HY-122152CASNo.:27007-85-8Synonyms:APY-606;Clospirazinehydrochloride分?式:C??H??Cl?N?OS?分?量:482.49作?靶點(diǎn):Ras作?通路:GPCR/GProtein儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Spiclomazinehydrochloride(APY-606)?種抗精神病藥和抗腫瘤藥。Spiclomazinehydrochloride抑制KRas。Spiclomazinehydrochloride誘導(dǎo)癌細(xì)胞凋亡(apoptosis)[1][2]。IC50&TargetK-RAS體外研究Spiclomazine(0-100μg/mL;24and48h)hydrochlorideinhibitscontact-independentcolonyformationofpancreaticcarcinomacellsinadose-dependentmanner[1].Spiclomazine(0.5xand1xIC50;48h)hydrochlorideinducesCFPAC-1andMIAPaCa-2cellsapoptosisinthemitochondrialpathway,andsignificantlyenhancedintracellularROSlevel[1].Spiclomazine(30μg/mL;24h)hydrochloridesuppressescellularmotilityinCFPAC-1andMIAPaCa-2cells[1].Spiclomazine(10and20μg/mL;24h)hydrochloridearrestscancercellcycleprogressionatG2phase[2].CellViabilityAssay[1]CellLine:CFPAC-1,MIAPaCa-2,HEK-293andHL-7702cellsConcentration:0-100μg/mLIncubationTime:24and48hResult:Resultedinatimeanddose-dependentgrowthreductionofCFPAC-1andMIAPaCa-2cells.ExhibitedlesscytotoxicitytonormalHEK-293andHL-7702cells.TheIC50for48h1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEtreatmentwas15.2±2.0μg/mL(31.5±2.0μM)forCFPAC-1,12.9±0.9μg/mL(26.8±0.9μM)forMIAPaCa-2,41.9±1.4μg/mL(86.9±1.4μM)forHEK-293,and71.2±3.3μg/mL(147.7±3.3μM)forHL-7702,respectively.ApoptosisAnalysis[1]CellLine:CFPAC-1andMIAPaCa-2cellsConcentration:7.6and15.2μg/mLforCFPAC-1,6.45and12.9μg/mLforMIAPaCa-2IncubationTime:48hResult:Increasedearlyapoptoticcells.WesternBlotAnalysis[1]CellLine:CFPAC-1andMIAPaCa-2cellsConcentration:10,20and30μg/mLIncubationTime:24hResult:Thecleavagesofcaspase-3/9wereincreasedinadose-dependentmanner.TheexpressionofBaxwasup-regulatedconcomitantwiththerelatedattenuationofBcl-2proteinexpression.Thelevelofcytochromecincytosolwasincreasedaccompaniedbythedecreaseofthelevelofcytochromecinmitochondria.CellMigrationAssay[1]CellLine:CFPAC-1andMIAPaCa-2cellsConcentration:30μg/mLIncubationTime:24hResult:Markedlysuppressedthemigrationofbothpancreaticcarcinomacells.CellInvasionAssay[1]CellLine:CFPAC-1andMIAPaCa-2cellsConcentration:30μg/mLIncubationTime:24hResult:Suppressedtheinvasionbydown-regulatingtheexpressionofMMP-2/9.CellCycleAnalysis[2]2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:MIAPaCa-2,CFPAC-1,BxPC-3,Capan-1andSW1990cellsConcentration:10and20μg/mLIncubationTime:24hResult:PromotedcancercellcyclearrestateitherG2phaseinMIAPaCa-2,CFPAC-1,andBxPC-3celllinesorSphaseinCapan-1andSW1990celllines.體內(nèi)研究Spiclomazine(68mg/kg;i.p.;everyotherdayfortwoweeks)hydrochloridereducesthegrowthofMIAPaCa-2xenograftinmice[2].AnimalModel:BALB/cmice,MIAPaCa-2xenograftmodel[2]Dosage:68mg/kgAdministration:Intraperitonealinjection,everyotherdayfortwoweeksResult:Completelyblockedthegrowthoftumorsinthreeofthefivemice.REFERENCES[1].ZhaoW,etal.Spiclomazineinducesapoptosisassociatedwiththesuppressionofcellviability,migrationandinvasioninpancreaticcarcinomacells.PLoSOne.2013Jun20;8(6):e66362.[2].GuoX,etal.Spiclomazinedisplaysapreferentialanti-tumoractivityinmutantKRas-drivenpancreaticcancer.Oncotarget.2018Jan8;9(6):6938-6951.McePdfHeightCaution:Prod