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N-氨基甲酰-L-谷氨酸性质、用途与生产工艺用途N-氨基甲酰-L-谷氨酸已显示出对氨中毒具有保护作用,并用于治疗急性高氨血症。生物活性Carglumicacid(N-Carbamyl-L-glutamicacid)是N-乙酰谷氨酸(NAG)的功能类似物和氨甲酰磷酸合成酶1(CPS1)的活化剂,用于研究与N-乙酰谷氨酸合成酶(NAGS)缺陷相关的急性和慢性高氨血症。靶点CPS1体外研究Carglumicacidsuppressescellviabilityinthepancreaticductaladenocarcinomacelllines,triple-negativebreastcancercelllines,hepatomacelllines,andhumannon-smallcelllungcarcinomacelllinesinadose-dependentmanner.The50%inhibitoryconcentration(IC50)ofCarglumicacidagainstthosecelllinesisbetween5and7.5mM.TheresultsshowthatCarglumicaciddoesnotinducecompletecellcyclearrest.Instead,therearemoresub-G1cellsamongCarglumicacid-treatedAsPC1andMDA-MB-231cellsthanamonguntreatedcells.InAsPC1andHPDE-E6E7cells,theIC50sofCarglumicacidare5mMandover10mM,respectively.InMDA-MB-231andMCF-12Acells,theIC50sofCarglumicacidare5mMand6mM,respectively.体内研究TheresultsshowthatCarglumicacid,butnotthevehiclecontrol,markedlyinhibitstumorgrowth.Intheorthotopicpancreaticcancermodel,tumorgrowthinhibitionbyCarglumicacidonday21is80%(P<0.01).Intheorthotopictriple-negativebreastcancermodel,tumorgrowthinhibitionbyCarglumicacidonday20is82%(P<0.01).TheseresultsindicatethatCarglumicacidsuppressestumorgrowthinpancreaticcancerandtriple-negativebreastcancer.Onday20,meantumorgrowthinhibitioninorallyandintravenouslytreatedmiceis55%and93%,respectively,relativetountreatedmice(P<0.01).
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关键字: N-氨基甲酰-L-谷氨酸;1188-38-1;N-CARBAMYL-L-GLUTAMI;
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