In vitro screening for chemokine antagonists

Chemokines play an important role in host defense coordinating the migration of immune cells. They do this by activating G-protein-coupled receptors and these proteins have attracted a huge investment in research and development by the pharmaceutical industry with the promise of new therapeutics for treating inflammatory diseases.

Here, we provide a brief perspective of the in vitro assays that have been used in drug discovery for identifying potent and specific chemokine receptor antagonists. We outline the complexity of the chemokine system, give a historical perspective on the in vitro assays and types of assays used at different stages of discovery, followed by several examples of successes and failures in the clinic.

We discuss the rationale for continuing, after several failures, targeting chemokine receptors and how screening may change with the increasing evidence of dimerization of chemokine receptors.