Identification of novel agonists of the integrin CD11b/CD18
We report the identification of novel small molecule agonists of integrin CD11b/CD18, which increased, in a dose-dependent manner, the adhesion of the integrin CD11b/CD18 expressing cells to two physiologically relevant ligands: Fibrinogen and iC3b. Compound 6 showed an ex vivo EC50 of 10.5 μM and in vitro selectivity for binding to the recombinant αA-domain of CD11b/CD18. In silico docking experiments suggest that the compounds recognized a hydrophobic cleft in the ligand-binding αA-domain, implying an allosteric mechanism of modulation of integrin affinity by this novel compound.
Faridi, Mohd. Hafeez; Maiguel, Dony; Barth, Constantinos J.; Stoub, Darren; Day, Ruth; Schürer, Stephan; and Gupta, Vineet, "Identification of novel agonists of the integrin CD11b/CD18" (2009). Student-Faculty Collaborative Research Publications. 18.
Bioorganic and Medicinal Chemistry Letters