IDrugs. 2010 Jul;13(7):472-781.

GSK-1605786, a selective small-molecule antagonist of the CCR9 chemokine receptor for the treatment of Crohn's disease.

Source

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.

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.

PMID:: 20582872; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances

Publication Types

Review

MeSH Terms

Substances

LinkOut - more resources

Medical

Libraries

LinkOut Holdings

Supplemental Content

Save items

Related citations in PubMed

Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. [J Pharmacol Exp Ther. 2010]
Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease.
Walters MJ, Wang Y, Lai N, Baumgart T, Zhao BN, Dairaghi DJ, Bekker P, Ertl LS, Penfold ME, Jaen JC, et al. J Pharmacol Exp Ther. 2010 Oct; 335(1):61-9. Epub 2010 Jul 21.
CCR9-positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease. [Gastroenterology. 2001]
CCR9-positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease.
Papadakis KA, Prehn J, Moreno ST, Cheng L, Kouroumalis EA, Deem R, Breaverman T, Ponath PD, Andrew DP, Green PH, et al. Gastroenterology. 2001 Aug; 121(2):246-54.
Role of beta7 integrin and the chemokine/chemokine receptor pair CCL25/CCR9 in modeled TNF-dependent Crohn's disease. [Gastroenterology. 2008]
Role of beta7 integrin and the chemokine/chemokine receptor pair CCL25/CCR9 in modeled TNF-dependent Crohn's disease.
Apostolaki M, Manoloukos M, Roulis M, Wurbel MA, Müller W, Papadakis KA, Kontoyiannis DL, Malissen B, Kollias G. Gastroenterology. 2008 Jun; 134(7):2025-35. Epub 2008 Mar 5.
Review CCR9 and inflammatory bowel disease. [Expert Opin Ther Targets. 2009]
Review CCR9 and inflammatory bowel disease.
Koenecke C, Förster R. Expert Opin Ther Targets. 2009 Mar; 13(3):297-306.
Review Chemokines as novel therapeutic targets for inflammatory bowel disease. [Ann N Y Acad Sci. 2009]
Review Chemokines as novel therapeutic targets for inflammatory bowel disease.
Nishimura M, Kuboi Y, Muramoto K, Kawano T, Imai T. Ann N Y Acad Sci. 2009 Sep; 1173:350-6.

See reviews... See all...

Cited by 3 PubMed Central articles

Shining a light on intestinal traffic. [Clin Dev Immunol. 2012]
Shining a light on intestinal traffic.
Murphy CT, Nally K, Shanahan F, Melgar S. Clin Dev Immunol. 2012; 2012:808157. Epub 2011 Nov 22.
Emerging Concepts and Approaches for Chemokine-Receptor Drug Discovery. [Expert Opin Drug Discov. 2010]
Emerging Concepts and Approaches for Chemokine-Receptor Drug Discovery.
O'Hayre M, Salanga CL, Handel TM, Hamel DJ. Expert Opin Drug Discov. 2010 Nov; 5(11):1109-1122.
Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation. [Arthritis Res Ther. 2010]
Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation.
Schmutz C, Cartwright A, Williams H, Haworth O, Williams JH, Filer A, Salmon M, Buckley CD, Middleton J. Arthritis Res Ther. 2010; 12(4):R161. Epub 2010 Aug 25.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

GSK-1605786, a selective small-molecule antagonist of the CCR9 chemokine recepto...
GSK-1605786, a selective small-molecule antagonist of the CCR9 chemokine receptor for the treatment of Crohn's disease.
IDrugs. 2010 Jul ;13(7):472-781.

PubMed
Channeling bias in the interpretation of drug effects.
Channeling bias in the interpretation of drug effects.
Stat Med. 1991 Apr ;10(4):577-81.

PubMed
Early combination disease-modifying antirheumatic drug therapy and tight disease...
Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial.
Arthritis Res Ther. 2010 ;12(3):R122. Epub 2010 Jun 24 .

PubMed
Effect of enalapril on survival in patients with reduced left ventricular ejecti...
Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators.
N Engl J Med. 1991 Aug 1 ;325(5):293-302.

PubMed
Effectiveness and safety of adalimumab in patients with ankylosing spondylitis o...
Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy.
Arthritis Res Ther. 2010 ;12(3):R117. Epub 2010 Jun 16 .

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: