Identification of novel agonists of the integrin CD11b/CD18

MH Faridi, D Maiguel, CJ Barth, D Stoub, R Day… - Bioorganic & medicinal …, 2009 - Elsevier
MH Faridi, D Maiguel, CJ Barth, D Stoub, R Day, S Schürer, V Gupta
Bioorganic & medicinal chemistry letters, 2009Elsevier
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 …
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 10.5μM 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.
Elsevier