Laflunimus_product_DataBase

Bioactivity

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].

Invitro

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]. Animal Model:

Name

Laflunimus

CAS

147076-36-6

Formula

C15H13F3N2O2

Molar Mass

310.27

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

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. [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.

PeptideDB

Laflunimus

CAS: 147076-36-6 F: C15H13F3N2O2 W: 310.27