AZ10397767-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAZ10397767Cat.No.:HY-124056CASNo.:333742-63-5分⼦式:C₁₅H₁₄ClFN₄O₂S₂分⼦量:400.88作⽤靶点:CXCR作⽤通路:GPCR/GProtein;Immunology/Inflammation储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性AZ10397767⼀种具有⼝服活性的、选择性CXCR2受体拮抗剂，IC50为1nM。AZ10397767减弱Oxaliplatin(HY-17371)诱导的NF-κB转录活性并增强Oxaliplatin诱导的雄激素⾮依赖性前列腺癌(AIPC)细胞凋亡。AZ10397767显抑制中性粒细胞募集到肿瘤中，从⽽在体外和体内对肿瘤⽣长产⽣不利响。IC50&TargetCXCR21nM(IC50)体外研究AZ10397767(20nM;48h)abrogatestheIL-8-induced(3nM)increaseinproliferation,reducingcellnumbertobelowbasallevels[2].AZ10397767(20nM;72h)increasesOxaliplatin(HY-17371)cytotoxicity,andpotentiatesOxaliplatin-inducedapoptosisinAIPCcells.AZ10397767byitselffailstoinduceapoptosisineitherPC3orDU145cells[3].AZ10397767(20nM;24h)attenuatestheOxaliplatin-inducedNF-κBtranscriptionalactivityandtheincreasesinmRNAtranscriptlevelsforeachoftheCXC-chemokines(CXCL8andCXCL1)andantiapoptoticgenes(Bcl-2andsurvivin)inthePC3andDU145cells[3].CellProliferationAssay[2]CellLine:LNCaPcellsand22Rv1cellsConcentration:20nMIncubationTime:48hResult:AbrogatedtheIL-8-induced(3nM)increaseinproliferation,reducingcellnumberto1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEbelowbasallevels.ApoptosisAnalysis[3]CellLine:PC3orDU145cellsConcentration:20nMIncubationTime:72hResult:Coadministrationwith0.1or1μMOxaliplatinresultedinamarkedincreaseinthesub-G0/G1cellpopulationineithercellline.PotentiatesOxaliplatin-inducedapoptosisinAIPCcells.RT-PCR[3]CellLine:PC3orDU145cellsConcentration:20nMIncubationTime:24hResult:AttenuatedtheOxaliplatin(1μM)-inducedNF-κBtranscriptionalactivityandtheincreasesinmRNAtranscriptlevelsforeachoftheCXC-chemokines(CXCL8andCXCL1)andantiapoptoticgenes(Bcl-2andsurvivin)inthePC3andDU145cells.体内研究AZ10397767(100mg/kg;Orally;twicedaily;for22days)displayreducedneutrophilinfiltrationaccompaniedwithretardationintumorgrowthinA549xenografttumors[4].AZ10397767(compound30a)hasaCLof4ml/min/kginrat[1].AnimalModel:SCIDmicewithA549cells[4]Dosage:100mg/kgAdministration:Orally;twicedaily;for22daysResult:Tumorswere36%smallerthantheircontrolcounterparts.Significantly(p<0.01)reducedthenumberoftumor-infiltratingneutrophilscomparedtomicereceivingvehiclecontrol.REFERENCES[1].IainWalters,etal.EvaluationofaseriesofbicyclicCXCR2antagonists.BioorgMedChemLett.2008Jan15;18(2):798-803.[2].AngelaSeaton,etal.Interleukin-8signalingpromotesandrogen-independentproliferationofprostatecancercellsviainductionofandrogenreceptorexpressionandactivation.Carcinogenesis.2008Jun;29(6):1148-56.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[3].CatherineWilson,etal.Chemotherapy-inducedCXC-chemokine/CXC-chemokinereceptorsignalinginmetastaticprostatecancercellsconfersresistancetooxaliplatinthroughpotentiationofnuclearfactor-kappaBtranscriptionandevasionofapoptosis.JPharmacolExpTher.2008Dec;327(3):746-59.[4].SimonTazzyman,etal.InhibitionofneutrophilinfiltrationintoA549lungtumorsinvitroandinvivousingaCXCR2-specificantagonistisassociatedwithreducedtumorgrowth.IntJCancer.2011Aug15;129(4):847-58.McePdfHeightCaution:Producthasno