Identification of novel agonists of the integrin CD11b/CD18

Mohd Hafeez Faridi, Dony Maiguel, Constantinos J. Barth, Darren Stoub, Ruth Day, Stephan Schürer, Vineet Gupta

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6902-6906
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number24
DOIs
StatePublished - Dec 15 2009

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Keywords

  • Agonist
  • CD11b/CD18
  • Cell-adhesion
  • Cell-based assay
  • High-throughput screening
  • Inflammation
  • Integrin
  • Mac-1

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Faridi, M. H., Maiguel, D., Barth, C. J., Stoub, D., Day, R., Schürer, S., & Gupta, V. (2009). Identification of novel agonists of the integrin CD11b/CD18. Bioorganic and Medicinal Chemistry Letters, 19(24), 6902-6906. https://doi.org/10.1016/j.bmcl.2009.10.077