High-throughput Screening Based Identification of Small Molecule Antagonists of Integrin CD11b/CD18 Ligand Binding

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2010 Mar 2

PMID 20188705

Citations 6

Authors

Mohd Hafeez Faridi

Dony Maiguel

Brock T Brown

Eigo Suyama

Constantinos J Barth

Michael Hedrick

Stefan Vasile

Eduard Sergienko

Stephan Schurer

Vineet Gupta

Affiliations

Soon will be listed here.

Abstract

Binding of leukocyte specific integrin CD11b/CD18 to its physiologic ligands is important for the development of normal immune response in vivo. Integrin CD11b/CD18 is also a key cellular effector of various inflammatory and autoimmune diseases. However, small molecules selectively inhibiting the function of integrin CD11b/CD18 are currently lacking. We used a newly described cell-based high-throughput screening assay to identify a number of highly potent antagonists of integrin CD11b/CD18 from chemical libraries containing >100,000 unique compounds. Computational analyses suggest that the identified compounds cluster into several different chemical classes. A number of the newly identified compounds blocked adhesion of wild-type mouse neutrophils to CD11b/CD18 ligand fibrinogen. Mapping the most active compounds against chemical fingerprints of known antagonists of related integrin CD11a/CD18 shows little structural similarity, suggesting that the newly identified compounds are novel and unique.

Citing Articles

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