Laflunimus

Laflunimus (HR325) is an immunosuppressive agent and an analogue of the Leflunomide-active metabolite A77 1726. Laflunimus is an orally active inhibitor of dihydroorotate dehydrogenase (DHODH). Laflunimus suppresses immunoglobulin (Ig) secretion, with IC₅₀ values of 2.5 and 2 µM for IgM and IgG, respectively. Laflunimus also is a prostaglandin endoperoxide H synthase (PGHS) -1 and -2 inhibitor^[1][2]. In Vitro: Ig secretion from mouse splenocytes was induced by lipopolysaccharide (LPS) for 5 days. Laflunimus inhibited the secretion of IgM and IgG with IC₅₀ values of 2.5 and 2 µM , respectively. Adding Uridine (50 µ M) increased these values to 70 and 60 µ M, respectively. Laflunimus inhibits LPS-induced kappa light-chain cell surface expression on 70Z/3 cells, a property also reversed by uridine^[1].
Laflunimus (HR325) is more potent than A77 1726 as an inhibitor of PGHS in guinea pig polymorphonuclear leukocytes (IC₅₀= 415 and 4400 nM, respectively) and on isolated ovine PGHS-1 (IC₅₀=64 and 742 µM) and PGHS-2 (IC₅₀=100 and 2766 µM)^[2]. In Vivo: HR325 (50 mg/kg; p.o.; days 14-18 after being injected with SRBC) inhibits the secondary anti-sheep red blood cell (SRBC) antibody response with ID₅₀ values of 38 mg/kg^[1].