Pharmacopeia Inc (PRINCETON, New Jersey), a clinical development stage biopharmaceutical company dedicated to discovering and developing novel small molecule therapeutics, announced the advancement of PS031291, a potent and highly selective oral antagonist at the chemokine receptor CCR1, as a preclinical development compound from its internal CCR1 discovery program. The chemokine receptor CCR1 has been implicated to play a significant role in multiple inflammatory and autoimmune disease processes. PS031291 has been shown in preclinical studies to be potent at both binding to CCR1 and at antagonizing CCR1-mediated chemotaxis. Pharmacopeia believes the compound may possess significant potential in the oral treatment of various inflammatory diseases including rheumatoid arthritis, multiple sclerosis, and psoriasis. The company intends to initiate Good Laboratory Practice toxicology studies on the compound in the 1st quarter of 2008.

A number of compounds discovered by Pharmacopeia are being developed by its various collaborators including Bristol-Myers Squibb Co; Celgene Corp; Cephalon, Inc; GlaxoSmithKline; Schering-Plough Corp; and Wyeth Pharmaceuticals. Nonetheless, PS031291 is the first compound to emerge from Pharmacopeia's internal drug discovery efforts into its internal development portfolio.

CCR1 is a member of the chemokine receptor family and is involved in the trafficking of T-cells and monocytes to specific sites of inflammation, such as the arthritic synovium and the myelin sheath. CCR1 is expressed on multiple cell types including monocytes, T-cells, dendritic cells, eosinophils and neutrophils, and is a major factor in mediating inflammatory responses through direct effects on leukocyte chemotaxis and Th1/Th2 cytokine balance. Multiple ligands interact with CCR1 with high affinity including MIP-1α (CCL3), RANTES (CCL5), MCP-2 3 (CCL8/7) plus several others. PS031291 is potent (IC50 = 0.0006 μM) in the human monocyte chemotaxis assay, potent (IC50 = 4nM) in the clinically relevant CCR1 internalization assay in human whole blood, and possesses a favorable pharmacokinetic profile.