Alpha 4 Integrin Antagonists

Author: Jackson, D.Y.

Source: Current Pharmaceutical Design, Volume 8, Number 14, 1 June 2002 , pp. 1229-1253(25)

Publisher: Bentham Science Publishers

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content

Abstract:

The accumulation of leukocytes in various organs contributes to the pathogenesis of a number of human autoimmune diseases such as asthma, rheumatoid arthritis, Crohn's disease, ulcerative colitis, hepatitis C, and multiple sclerosis. The inflammatory processes leading to tissue damage and disease are mediated in part by the agr4 integrins, agr4bgr1 and agr4bgr7, expressed on the leukocyte cell surface. These glycoprotein receptors modulate cell adhesion via interaction with their primary ligands, vascular cell adhesion molecule (VCAM) and mucosal addressin cell adhesion molecule (MAdCAM), expressed in the affected tissue. Upon binding, the combined integrin / CAM interactions at the cell surface result in firm adhesion of the leukocyte to the vessel wall followed by entry into the affected tissue. Elevated cell adhesion molecule (CAM) expression in various organs has been linked with several autoimmune diseases. Monoclonal antibodies specific for agr4 integrins or their CAM ligands can moderate inflammation in animal models suggesting such inhibitors may be useful for treating human inflammatory diseases. The agr4 integrins have become well validated drug targets for pharmaceutical companies and numerous publications describing agr4 integrin antagonists have recently appeared. This article discusses the rationale for targeting agr4 integrins for the treatment of autoimmune disorders and reviews some currently known antagonists. The methods used to identify lead molecules and the progress of selected antagonists toward becoming new drugs will is also discussed. (131 references).

Keywords: alpha 4 integrin; alpha 4 beta 1 antagonist; vcam; mad cam

Document Type: Review article

DOI: 10.2174/1381612023394737

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$55.10 plus tax      Refund Policy

 

OR

Back to top

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content
Share this item with others: These icons link to social bookmarking sites where readers can share and discover new web pages.
Page Help Click here for Page Help
Shopping cart
Tools
Sign in






Need to register?
Sign up here
Text size: A | A | A | A