Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10765053 | Biochemical and Biophysical Research Communications | 2010 | 6 Pages |
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.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Mohd Hafeez Faridi, Dony Maiguel, Brock T. Brown, Eigo Suyama, Constantinos J. Barth, Michael Hedrick, Stefan Vasile, Eduard Sergienko, Stephan Schürer, Vineet Gupta,