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 IC
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Product Description
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 IC 50 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.
In Vitro
Ig secretion from mouse splenocytes was induced by lipopolysaccharide (LPS) for 5 days. Laflunimus inhibited the secretion of IgM and IgG with IC 50 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. Laflunimus (HR325) is more potent than A77 1726 as an inhibitor of PGHS in guinea pig polymorphonuclear leukocytes (IC 50 = 415 and 4400 nM, respectively) and on isolated ovine PGHS-1 (IC 50 =64 and 742 µM) and PGHS-2 (IC 50 =100 and 2766 µM). MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 ID 50 values of 38 mg/kg . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male CD-1 mice (20-24 g) Dosage: 50 mg/kg Administration: Oral; days 14-18 after being injected with SRBC Result: The level of circulating anti-SRBC IgG in this model was inhibited dose relatedly by orally administered HR325.
Names and Identifiers
Smiles
O=C(NC1=CC=C(C(F)(F)F)C(C)=C1)/C(C#N)=C(C2CC2)\\O
Molecular Weight
310.27
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