The new salicylate derivative UR-1505 modulates the Th2/humoral response in a dextran sodium sulphate model of colitis that resembles ulcerative colitis.

The aim of the present study was to evaluate the inmunomodulatory effects of UR-1505, a new salicylate derivative, on the T helper (Th)2/humoral response produced during dextran sodium sulfate (DSS)-induced rat colitis. In the in vitro studies, UR-1505 (300 microM) inhibited both the production of interleukin (IL)-10 and IL-5 in concanavalin A (Con A)-activated splenocytes and the production of immunoglobulin (Ig) G and IgA by B-lymphocytes. However, in contrast to the in vitro results, the administration of UR-1505 (10 and 30 mg/kg per day) to rats with established DSS-colitis enhanced both IL-10 and IgA production, whereas it inhibited IgG production, thus ameliorating the intestinal inflammation.

UR-1505, a salicylate able to selectively block T-cell activation, shows intestinal anti-inflammatory activity in the chronic phase of the DSS model of rat colitis.

Background: UR-1505 is a novel salicylate derivative compound that has been demonstrated to selectively down-regulate T-cell activation. The aim of the present study was to elucidate the mechanisms involved in the intestinal anti-inflammatory effects of UR-1505 in 2 protocols of a dextran sodium sulfate (DSS) model of rat colitis: acute and established colitis.

Methods: The first protocol consisted of incorporating DSS into the drinking water at a concentration of 5% (w/v) for 5 days (acute initial colitis).

UR-1505, a new salicylate, blocks T cell activation through nuclear factor of activated T cells.

2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a new molecule chemically related to salicylic acid, has immunomodulator properties and is currently under clinical development for treatment of atopic dermatitis. The present work describes the immunomodulatory profile of UR-1505. UR-1505 targets T cells, inhibiting their proliferation and cytokine production by blocking nuclear factor of activated T cells (NF-AT) DNA-binding activity.