Laflunimus

• CAT Number: R060434
• CAS Number: 147076-36-6
• Molecular Formula: C15H13F3N2O2
• Molecular Weight: 310.27
• Purity: ≥95%
• Synonyms: (Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[3-methyl-4-(trifluoromethyl)phenyl]prop-2-enamide
• InChI: InChI=1S/C15H13F3N2O2/c1-8-6-10(4-5-12(8)15(16,17)18)20-14(22)11(7-19)13(21)9-2-3-9/h4-6,9,21H,2-3H2,1H3,(H,20,22)/b13-11-
• InChIKey: GDHFOVCRYCPOTK-QBFSEMIESA-N
• SMILES: CC1=C(C=CC(=C1)NC(=O)C(=C(C2CC2)O)C#N)C(F)(F)F

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].
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].
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].

Reference

[1]. Thomson TA, et al. In vitro and in Vivo inhibition of immunoglobulin secretion by the immunosuppressive compound HR325 is reversed by exogenous uridine. Scand J Immunol. 2002 Jul;56(1):35-42.
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[2]. Curnock AP, et al. Potencies of leflunomide and HR325 as inhibitors of prostaglandin endoperoxide H synthase-1 and -2: comparison with nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 1997 Jul;282(1):339-47.
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