Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEA-357300Cat.No.:HY-116861CASNo.:369358-07-6分子式:C??H??ClN?O?S分子量:359.87作用靶點(diǎn):MetAP作用通路:MetabolicEnzyme/Protease儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性A-357300是一種可逆且選擇性的MetAP2抑制劑，對(duì)MetAP2和MetAP1的IC50值分別為0.12μM和57μM。A-357300可選擇性地使內(nèi)皮細(xì)胞和部分腫瘤細(xì)胞的細(xì)胞周期阻滯于G1期，從而誘導(dǎo)細(xì)胞增殖。A-357300在體外和體內(nèi)均能抑制血管生成，并在癌、肉瘤和神經(jīng)母細(xì)胞瘤小鼠模型中顯示出強(qiáng)大的抗腫瘤活性。A-357300可用于神經(jīng)母細(xì)胞瘤、纖維肉瘤和乳腺癌的研究。體外研究A-357300(0.1nM-100μM,3days)exhibitsselectiveantiproliferativeactivityagainstendothelialcellsandtumorcellswithIC50sof0.1-2μM,butnotinhumanprimarycells[1].A-357300(10μM,3days)inducescytostasisbycellcyclearrestattheG1phaseinHMVECsorHT-1080cells[1].A-357300(0-10μM,1day)reducestheconcentrationofcyclinA,whilekeepingtheconcentrationofcyclinD1unchangedinHMVECs[1].A-357300(0.08-2μM,3days)completelyblockstheformationofthelumenataconcentrationof0.4μMinHMVECs[1].CellCycleAnalysis[1]CellLine:HMVECsandHT-1080cellsConcentration:10μMIncubationTime:3daysResult:ShowedG1phasearrest,withnoaccumulationofsub-G1phasecells.WesternBlotAnalysis[1]1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:HMVECsConcentration:0,0.001,0.01,0.1,1and10μMIncubationTime:24hResult:ReducedtheconcentrationofcyclinA,whilekeepingtheconcentrationofcyclinD1unchanged.體內(nèi)研究A-357300(25-100mg/kg,s.c.,twicedailyfor7days)showsinhibitionofmousecorneaangiogenesis[1].A-357300(8-100mg/kg,s.c.,onceeveryotherdayortwicedailyfor14-24days)inhibitsthegrowthofneuroblastoma,fibrosarcomaandbreastcancerinmice[1].AnimalModel:CornealangiogenesismodelestablishedinCF1mice[1]Dosage:25,75and100mg/kgAdministration:Subcutaneousinjection(s.c.),twicedailyfor7daysResult:Inhibitedgrowthfactor-inducedcorneaneovascularizationinadose-dependentmanneragainstVEGF,andagainstbFGF.AnimalModel:CHP-134neuroblastomaxenograftmodelestablishedinmice[1]Dosage:100mg/kgAdministration:Subcutaneousinjection(s.c.),twicedailyfor24daysResult:SignificantlysuppressedgrowthofthisestablishedtumorxenograftwithaT/Cof0.185onday24aftertheinitiationoftreatment.AnimalModel:HT-1080fibrosarcomaxenograftmodelestablishedinSCID-beigemice[1]Dosage:15,30,60and100mg/kgAdministration:Subcutaneousinjection(s.c.),twicedailyfor14-16daysResult:Inhibitedtumorgrowthinadose-dependentmannerandnoovertsignsoftoxicitywereobserved.AnimalModel:MDA-435-LMbreastcancerxenograftmodelestablishedinSCIDmice[1]Dosage:8,16,20mg/kg(group1);50and100mg/kg(group2)Administration:Subcutaneousinjection(s.c.),onceeveryotherday(group1)ortwicedaily(group2)for20days2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult: Exhibitedbetterefficacyingroup2thangroup1.REFERENCESWangJ,ETAL.Tumorsuppressionbyarationallydesignedreversibleinhibitorofmethionineaminopeptidase-2.CancerRes.2003Nov15;63(22):7861-9.McePdfHeightCaution:Producthasnotbeenfullyvali