Rational design of CCR2 antagonists: a survey of computational studies

Abstract

Importance of the field: CC-chemokine receptor 2 (CCR2) belongs to the GPCR superfamily and is the primary receptor for monocyte chemoattractant protein-1 (MCP-1), also known as chemokine ligand CCL2. Studies indicate the possible involvement of MCP-1 and CCR2 in various disease conditions, such as rheumatic arthritis, multiple sclerosis, vascular diseases, obesity and diabetes, via the inflammatory pathway. MCP-1 and CCR2 knockout mice under a broad range of stimuli exhibit deficient monocyte recruitment suggesting its potential role in inflammation. Overall, there is evidence that an impairment of monocyte trafficking in inflammation models occurs when there is a loss of MCP-1 effector function. This makes its receptor, CCR2, an attractive target for pharmaceutical research. Several small molecular CCR2 antagonists have been developed, particularly in the industry.Areas covered in this review: In this article, we have summarized the in silico work carried out in the area of CCR2 and reviewed mainly the computer aided drug design (CADD) studies reported on quantitative structure–activity relationship, homology modeling, molecular docking and virtual screening.What the reader will gain: A survey of computational studies for the rational design and development of CCR2 antagonists.Take home message: CADD tools can be used to rationalize the identification of the potential leads and these techniques can be effectively applied in the rapid searching of novel and potent CCR2 antagonists.