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Updated: Jul 19, 2026

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs
Published on: February 2, 2024
A small molecule agonist of an integrin, alphaLbeta2
Wei Yang1, Christopher V Carman, Minsoo Kim
1CBR Institute for Biomedical Research, Departments of Pathology and Anesthesia, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
The binding of integrin alpha(L)beta(2) to its ligand intercellular adhesion molecule-1 is required for immune responses and leukocyte trafficking. Small molecule antagonists of alpha(L)beta(2) are under intense investigation as potential anti-inflammatory drugs. We describe for the first time a small molecule integrin agonist. A previously described alpha/beta I allosteric inhibitor, compound 4, functions as an agonist of alpha(L)beta(2) in Ca(2+) and Mg(2+)and as an antagonist in Mn(2+). We have characterized the mechanism of activation and its competitive and noncompetitive inhibition by different compounds. Although it stimulates ligand binding, compound 4 nonetheless inhibits lymphocyte transendothelial migration. Agonism by compound 4 results in accumulation of alpha(L)beta(2) in the uropod, extreme uropod elongation, and defective de-adhesion. Small molecule integrin agonists open up novel therapeutic possibilities.
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