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来氟米特是一种新型抗炎及免疫抑制剂,对多种自身免疫性疾病有治疗作用,在器官移植动物模型上显示抑制排异反应。其作用机制是抑制蛋白酪氨酸激酶以及嘧啶从头生物合成途径中的二氢乳清酸脱氢酶的活性。期临床试验显示,治疗类风湿性关节炎效果显著,但其活性代谢物A771726在人体内的t1/2长达15～18d,因而用于移植病人时剂量调整困难。A771726的丙二腈酰胺类似物MNA279和MNA715在临床前试验中显示出很强的免疫抑制作用
Leflunomide is a novel anti-inflammatory and immunosuppressive agent that has a therapeutic effect on a variety of autoimmune diseases and shows an anti-rejection response in animal models of organ transplantation. Its mechanism of action is to inhibit the activity of the protein tyrosine kinase as well as the dihydroorotate dehydrogenase in the pyrimidine de novo biosynthesis pathway. Phase clinical trials show that the treatment of rheumatoid arthritis significant effect, but the active metabolite A771726 in the human body t1 / 2 as long as 15 ~ 18d, and therefore for the transplantation of patients dose adjustment difficult. The malononitrilamide analogs MNA279 and MNA715 of A771726 showed a strong immunosuppressive effect in preclinical experiments