α4-integrin

Carotegrast is a selective α4 integrin antagonist that inhibits the migration of inflammatory cells to the intestinal mucosa by blocking the interaction between α4β1/α4β7 integrins and their ligands. Carotegrast is used in research and clinical practice for the treatment of inflammatory bowel diseases such as ulcerative colitis; it exerts local anti-inflammatory effects and results in low systemic exposure.

Zaurategrast (CDP323) is a small-molecule prodrug antagonist that inhibits the interaction between vascular cell adhesion molecule 1 (VCAM-1) and α4-integrins, originally developed by Celltech plc for oral administration, and it serves as a valuable research compound for investigating leukocyte trafficking, immune cell adhesion, and therapeutic strategies relevant to multiple sclerosis.

Compound 11, an α4 integrin receptor antagonist, exhibits oral activity and functions as an antagonist of the α4 integrin receptor. It efficiently inhibits the adhesion of K562 cells mediated by the interactions of α4β1/VCAM-1 and α4β7/MAdCAM-1, with IC50 values of 130 nM and 2 nM, respectively. Compound 11 also shows potential for use in studies using the DSS (dextran sulfate sodium) induced colitis mouse model.

Natalizumab is a recombinant humanized monoclonal antibody and a humanized monoclonal antibody inhibitor that selectively targets α4 integrin (CD49d). Natalizumab binds to the α4β1 heterodimer and blocks its interaction with vascular cell adhesion molecule 1. Natalizumab also prevents lymphocytes from entering the central nervous system, thereby preventing acute demyelinating relapses, and is used in the study of relapsing-remitting multiple sclerosis and Crohn’s disease. Natalizumab possesses anti-inflammatory and immunomodulatory activity, inhibiting the adhesion, retention, and transendothelial migration of immune cells, and reducing the infiltration of inflammatory cells into the central nervous system or affected sites. Natalizumab is also being studied for autoimmune or inflammation-related diseases such as B-cell lymphoma and non-infectious uveitis.

6-B345TTQ is an α4 integrin inhibitor that can impede the interaction between α4 and Leupaxin. This compound is applicable for studies focused on inflammation research.

GW559090 is a selective, competitive, and high-affinity α4 integrin antagonist with a Kd value of 0.19 nM for α4β1. It effectively inhibits the binding of α4β1 to vascular cell adhesion molecule 1 (VCAM-1) and fibronectin, with IC50 values of 7.72 and 8.04 nM, respectively. Additionally, GW559090 suppresses the interaction between α4β7 and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with an IC50 value of 23 nM. It also inhibits inflammatory infiltration in the eye, repairs the corneal barrier, and restores goblet cell function, making it useful for research into dry eye syndrome associated with Sjögren's syndrome.

Carotegrast methyl (AJM300), an orally-active small molecule, can antagonize the α4 integrin receptor. It is a specific and dual α4β1/α4β7 integrin antagonist.

TBC-3486 is a novel potent inhibitor of integrin α4, being 200-fold more potent in inhibiting α4β1 than α4β7.

Carotegrast methyl, also known as AJM300 and PTC-100, is an orally-active small molecule that antagonises the α4 integrin receptor. AJM300 reduces inflammation by blocking leucocyte trafficking. Oral treatment with AJM300 dose-dependently inhibited lymphocyte homing to Peyer's patches and increased the peripheral lymphocyte count in the same dose range. AJM300 dose-dependently prevented the development of experimental colitis in mice.

EILEVPST, a recombinant human fibronectin-derived low-molecular-weight peptide fragment, promotes cell type-specific α4 integrin-mediated adhesion. It is utilized in thrombogenesis research [1].