A-357300-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEA-357300Cat.No.:HY-116861CASNo.:369358-07-6分子式:C₁₅H₂₂ClN₃O₃S分子量:359.87作用靶点:MetAP作用通路:MetabolicEnzyme/Protease储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性A-357300是一种可逆且选择性的MetAP2抑制剂，对MetAP2和MetAP1的IC50值分别为0.12μM和57μM。A-357300可选择性地使内皮细胞和部分肿瘤细胞的细胞周期阻滞于G1期，从而诱导细胞增殖。A-357300在体外和体内均能抑制血管生成，并在癌、肉瘤和神经母细胞瘤小鼠模型中显示出强大的抗肿瘤活性。A-357300可用于神经母细胞瘤、纤维肉瘤和乳腺癌的研究。体外研究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—您身边的抑制剂大师www.MedChemECellLine:HMVECsConcentration:0,0.001,0.01,0.1,1and10μMIncubationTime:24hResult:ReducedtheconcentrationofcyclinA,whilekeepingtheconcentrationofcyclinD1unchanged.体内研究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—您身边的抑制剂大师www.MedChemEResult: Exhibitedbetterefficacyingroup2thangroup1.REFERENCESWangJ,ETAL.Tumorsuppressionbyarationallydesignedreversibleinhibitorofmethionineaminopeptidase-2.CancerRes.2003Nov15;63(22):7861-9.McePdfHeightCaution:Producthasnotbeenfullyvali