9-cis-UAB30-9Z-UAB-30-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemE9-cis-UAB30Cat.No.:HY-129108CASNo.:205252-57-9Synonyms:(9Z)-UAB-30分子式:C₂₀H₂₂O₂分子量:294.39作用靶点:Oct3/4;Microtubule/Tubulin;E1/E2/E3Enzyme;Proteasome作用通路:StemCell/Wnt;CellCycle/DNADamage;Cytoskeleton;MetabolicEnzyme/Protease储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性9-cis-UAB30是一种rexinoid激动剂。9-cis-UAB30可显著降低患者来源异种移植瘤(PDX)的增殖、活力和迁移能力。9-cis-UAB30可诱导细胞周期阻滞，表现为G1期细胞比例显著增加和S期细胞比例显著降低，其机制是通过下调SKP2和/或20S蛋白酶体的活性，从而提高p27kip1蛋白的稳定性。9-cis-UAB30可下调干细胞标志物mRNA(Oct4、Nanog、Sox2、巢蛋白)的表达水平，并上调分化标志物mRNA(β3-tubulin、NSE、HOXC9、GAP43)的表达水平。在测试剂量下，9-cis-UAB30对中枢神经系统和心血管系统无不良反应。9-cis-UAB30可用于研究神经母细胞瘤、皮肤T细胞淋巴瘤和乳腺癌[1][2][3]。IC50&TargetSkp2体外研究9-cis-UAB30(0-50μM,96h)inducesneuriteoutgrowthinCOA6cellsaslowas10μM[1].9-cis-UAB30(0-100μM,96h)significantlyreducestheproliferationandsurvivalrateofCOA3andCOA6cells[1].9-cis-UAB30(25-50μM,3-7days)significantlyreducesthemigrationandinvasionabilitiesofCOA3andCOA6cells[1].9-cis-UAB30(0-50μM,24h)significantlyincreasestheproportionofG1phaseanddecreasestheproportionofSphaseinCOA3andCOA6cells,indicatingthatcellcyclearrestoccurredattheG1/Stransitionpoint[1].9-cis-UAB30(0-100μM,24-96h)significantlyreducesandeffectivelytargetsCD133-positiveorCD133-enrichedcellsinbothCOA3andCOA6cells[1].9-cis-UAB30(0-50μM,7days)significantlyreducesthenumberoftumorspheroidsformedinCOA3andCOA6cells[1].9-cis-UAB30(0-25μM,72h)significantlydownregulatesthemRNAabundanceofstemcellmarkers(Oct4,1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemENanog,Sox2,nestin)inCOA3andCOA6PDXcells,andupregulatesthemRNAabundanceofdifferentiationmarkers(β3-tubulin,NSE,HOXC9,GAP43)[1].9-cis-UAB30(5-50μM,42-48h)significantlyinhibitstheviabilityofMyLaandHuT78cellsafter24and48hoursoftreatment[2].9-cis-UAB30exhibitsstronginhibitoryactivityagainstCTCLcelllines,includingMyLacells(IC50=34.7μM),HuT78cells(IC50=34.7μM),andHHcells(IC50=34.7μM)[2].9-cis-UAB30(10-25μM,6-24h)increasesthep27kip1proteinlevelinMyLacells,HuT78cells,andHHcells,whiledecreasingtheSKP2proteinlevel[2].9-cis-UAB30(10-25μM,6-24h)doesnotchangethehomeostaticlevelofp27kip1mRNAinMyLacells,HuT78cellsandHHcells,butsignificantlyreducesthelevelofSKP2mRNA;CKS1BmRNAisunaffected[2].9-cis-UAB30(25μM,12-24h)inhibits20Sproteasomeactivity,buttheeffectvariedamongcelllines:significantinhibitionwasobservedinHuT78cellsat18-24h,inhibitionwasobservedinHHcellsat24h,andnosignificanteffectwasobservedinMyLacells[2].CellProliferationAssay[1]CellLine:COA3andCOA6PDXcellsConcentration:0μM,10μM,25μM,50μM,100μMIncubationTime:96hResult:SignificantlyreducedtheproliferationrateofCOA3andCOA6cells.RT-PCR[1]CellLine:COA3andCOA6PDXcellsConcentration:0μM,10μM,25μMIncubationTime:72hResult:DownregulatedthemRNAabundanceofstemcellmarkers(Oct4,Nanog,Sox2,nestin).UpregulatedthemRNAabundanceofdifferentiationmarkers(β3-tubulin,NSE,HOXC9,GAP43).CellViabilityAssay[2]CellLine:MyLacells,HuT78cellsConcentration:0μM,10μM,25μMIncubationTime:72hResult:InMyLacells,50μMreducedcellnumberwithin24hours;at48hours,both25μMand50μMinhibitedcellviability.InHuT78cells,5μMinhibitedcellviabilitywithin24hours.2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemE体内研究9-cis-UAB30(0-100mg/kg,p.o.,oncedailyfor28days)primarilytargetstheliverinrats.Theno-observed-adverse-effectlevel(NOAEL)withrepeated28-dayadministrationis3mg/kg/day,whiledosesof15-100mg/kgshowsomehepatotoxicity[3].9-cis-UAB30(0-100mg/kg,p.o.,oncedailyfor28days)doesnotproduceanytoxicityinbeaglesandhasnoadverseeffectsonthecentralnervoussystemandcardiovascularsystem[3].REFERENCESMarayatiR,etal.9-cis-9-cis-UAB30,anovelrexinoidagonist,decreasestumorigenicityandcancercellstemnessofhumanneuroblastomapatient-derivedxenografts.TranslOncol.2021Jan;14(1):100893.ChouCF,etal.TheretinoidXreceptoragonist,9-cisUAB30,inhibitscutaneousT-celllymphomaproliferationthroughtheSKP2-p27kip1axis.JDermatolSci.2018Jun;90(3):343-356.LindebladM,etal.Assessmentoforaltoxicityandsafetyof9-cis-UAB30,apotentialchemopreventiveagent,inratanddogstudies.DrugChemToxicol.2011Jul;34(3):300-10.KapetanovicIM,etal.Murineoncogenicityandpharmacokineticsstudiesof9-cis-UAB30,anRXRagonist,forbreastcancerchemoprevention.IntJTo