Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEOXPHOS-IN-2Cat.No.:HY-176284分子式:C??H??F?N?O?S分子量:588.6作用靶點(diǎn):OxidativePhosphorylation;MitochondrialMetabolism;Apoptosis;ReactiveOxygenSpecies(ROS);AMPK;Keap1-Nrf2作用通路:MetabolicEnzyme/Protease;Apoptosis;Immunology/Inflammation;NF-κB;Epigenetics;PI3K/Akt/mTOR儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性O(shè)XPHOS-IN-2是一種口服有效的OXPHOS抑制劑。OXPHOS-IN-2在PC9(IC50=12.3nM)和Bxpc-3細(xì)胞(在葡萄糖培養(yǎng)基中IC50=250nM，在半乳糖培養(yǎng)基中IC50=17.5nM)中表現(xiàn)出強(qiáng)烈的抑制活性。OXPHOS-IN-2調(diào)節(jié)NADH/NAD+比值并降低ATP水平。OXPHOS-IN-2通過激活活性氧(ROS)和下調(diào)Nrf2水平誘導(dǎo)腫瘤細(xì)胞凋亡(apoptosis)。OXPHOS-IN-2可用于癌癥如非小細(xì)胞肺癌和胰腺癌的研究[1]。體外研究OXPHOS-IN-2(Compound28c)(0-1000μM,12h)reducestheratioofATPandNAD+/NADHandinhibitsAMPKphosphorylationinPC9cells[1].OXPHOS-IN-2(0-20nM,14days)significantlyinhibitsthecolonyformingabilityofPC9cells[1].OXPHOS-IN-2(0-1μM)caninduceapoptosisbydosedependentlyincreasingreactiveoxygenspecies(ROS)levelsandreducingmitochondrialmembranepotentialinPC9andBxpc-3cells[1].OXPHOS-IN-2(0-50nM)inducesDNAdamageandincreasestheexpressionofγ-H2AXinPC9cells[1].OXPHOS-IN-2caninhibittheproliferationofvarioustumorcelllinesinglucoseandgalactosemedium,includingH1975(IC50=6.43nMand29.5nM),H2228(IC50=4.54nMand21.5nM),KP-4(IC50=3.61nMand48.7nM),MKN45(IC50=5.78nMand29.8nM),HCT116(IC50=5.19nMand31.2nM),MDA-MB-231(IC50=1.31nMand7.5nM),MHCC-97H(IC50=1.76nMand12.4nM)andSiHA(IC50=5.10nMand35.1nM)cells[1].ApoptosisAnalysis[1]CellLine:PC9spheresConcentration:1,10,20nM1/2 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIncubationTime:72hResult:Significantlyincreasedtheapoptosisrateofcells.WesternBlotAnalysis[1]CellLine:PC9cellsConcentration:1,10,50nMIncubationTime:12hResult:SignificantlyreducedthelevelofpAMPK.體內(nèi)研究OXPHOS-IN-2(Compound28c)(7.5mg/kg;p.o.;oncedaily;for14days)significantlyinhibitstumorgrowthandhasgoodsafetyinPC9modeledmaleBALB/c-numice[1].AnimalModel:5×107PC9cellsinjectedmaleBALB/c-numice(3-4weeks)[1]Dosage:7.5mg/kgAdministration:Oraladministration(p.o.);oncedailyfor14daysResult:Significantlyinhibitedtumorvolumeandtumorweight,superiortoIACS-010759(HY-112037).Didnotcausesignificantchangesinweight.SignificantlyreducedNAD+/NADHratioandATPcontent.REFERENCESCaoL,etal.Synthesisandevaluationofnew5-(1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazolederivativesandtheirapplicationasOXPHOSinhibitors.EurJMedChem.2025Jun25;297:117903.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappl