Title

Identification of novel agonists of the integrin CD11b/CD18

Document Type

Article

Publication Date

2009

Abstract

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.

Publication Title

Bioorganic and Medicinal Chemistry Letters

ISSN

0960-894X

DOI

http://dx.doi.org/10.1016/j.bmcl.2009.10.077

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