title: GSK-1605786, a selective small-molecule antagonist of the CCR9 chemokine receptor for the treatment of Crohn's disease.
abstract: GSK-1605786 (CCX-282; Traficet-EN), a selective antagonist of the CC chemokine receptor (CCR9), is being developed by GlaxoSmithKline plc under license from ChemoCentryx Inc for the potential treatment of inflammatory bowel disease, including Crohn's disease and celiac disease. CCR9 is a tissue-specific lymphocyte trafficking molecule that selectively attracts both B- and T-cells to the small gut. Inhibition of CCR9 by GSK-1605786 may inhibit B- and T-cell entry to the small gut and ameliorate inflammation while leaving immune function at other anatomical sites unaffected. GSK-1605786 was assessed as a treatment for moderate-to-severe Crohn's disease in the phase II/III PROTECT-1 trial and as a treatment for celiac disease in a phase II trial. Data suggest that GSK-1605786 is efficacious in patients with Crohn's disease with the advantage of being orally bioavailable.
authors.affiliation: University of Birmingham and the NIHR Biomedical Research Unit for Liver Disease, Centre for Liver Research, MRC Centre for Immune Regulation, The College of Medical and Dental Sciences, Queen Elizabeth Hospital Birmingham NHS Foundation Trust, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Bertus
authors.initials: B
authors.lastname: Eksteen
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002446:Celiac Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D054388:Receptors, CCR / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C119309:CC chemokine receptor 9; D015507:Drugs, Investigational; D054388:Receptors, CCR