Description
An immunosuppressive agent. Inhibits T and B cell proliferation. Activity is attributed mainly to its metabolite, a malononitrile derivative, which is beleived to inhibit dihydroorotate dehydrogenase as well as several protein tyrosine kinases. Therapeutically as a antirheumatic. In vitro the active metabolite A77 1726 (RS-61980) inhibits dihydroorotate dehydrogenase (Ki = 2.7 μM) and de novo pyrimidine synthesis in T-cells; blocks lymphocyte cell cycle progression and proliferation. A77 1726 also inhibits anti-CD3/CD28-induced cytokine production in PBMC cells (IC50 = 21-27 μg/ml). In vivo reduces inflammation in several animal models of autoimmune disease, arthritis, asthma and graft rejection.