A Simple,No-Wash Cell Adhesion–Based High-Throughput Assay for the Discovery of Small-Molecule Regulators of the Integrin CD11b/CD18

Abstract

The leukocyte-specific integrin CD11b/CD18 plays a key role in the biological function of these cells and represents a validated therapeutic target for inflammatory diseases. Currently, the low affinity interaction between CD11b/CD18 integrin and its respective ligand poses a challenge in the development of cell-based adhesion assays for the high-throughput screening (HTS) environment. Here the authors describe a simple cell-based adhesion assay that can be readily used for HTS for the discovery of functional regulators of CD11b/CD18. The assay consistently produces acceptable Z' values (> 0.5) for HTS. After testing the assay using 2 established blocking antibodies as reference biologicals, the authors performed a proof-of-concept primary screen using a library of 6612 compounds and identified both agonist and antagonist hits. (Journal of Biomolecular Screening 2007:406-417)

Keywords

integrin no-wash assay cell adhesion assay primary screen

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