High-throughput screening based identification of small molecule antagonists of integrin CD11b/CD18 ligand binding

Mohd Hafeez Faridi, Dony Maiguel, Brock T. Brown, Eigo Suyama, Constantinos J. Barth, Michael Hedrick, Stefan Vasile, Eduard Sergienko, Stephan Schürer, Vineet Gupta

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)194-199
Number of pages6
JournalBiochemical and biophysical research communications
Volume394
Issue number1
DOIs
StatePublished - Mar 26 2010

Keywords

  • Adhesion assay
  • CD11b/CD18
  • HTS assay
  • Inhibitor
  • Integrin
  • Screening

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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  • Cite this

    Faridi, M. H., Maiguel, D., Brown, B. T., Suyama, E., Barth, C. J., Hedrick, M., Vasile, S., Sergienko, E., Schürer, S., & Gupta, V. (2010). High-throughput screening based identification of small molecule antagonists of integrin CD11b/CD18 ligand binding. Biochemical and biophysical research communications, 394(1), 194-199. https://doi.org/10.1016/j.bbrc.2010.02.151