Therapeutic antibodies directed at G protein-coupled receptors

Abstract

G protein-coupled receptors (GPCRs) are one of the most important classes of targets for small molecule drug discovery, but many current GPCRs of interest are proving intractable to small molecule discovery and may be better approached with bio-therapeutics. GPCRs are implicated in a wide variety of diseases where antibody therapeutics are currently used. These include inflammatory diseases such as rheumatoid arthritis and Crohn disease, as well as metabolic disease and cancer. Raising antibodies to GPCRs has been difficult due to problems in obtaining suitable antigen because GPCRs are often expressed at low levels in cells and are very unstable when purified. A number of new developments in over-expressing receptors, as well as formulating stable pure protein, are contributing to the growing interest in targeting GPCRs with antibodies. This review discusses the opportunities for targeting GPCRs with antibodies using these approaches and describes the therapeutic antibodies that are currently in clinical development.

Figures and Tables

Figure 1 Opportunities for G protein-coupled receptor-targeted antibody therapeutics. Therapeutic areas in which G protein-coupled receptors (GPCRs) suitable as targets for antibody-based drugs have been identified. In total, 88/370 GPCRs have strong disease rationale and a profile suitable for targeting with an antibody.

Table 1 Antigen formats used to generate G protein-coupled receptor targeted antibodies

Table 2 G protein-coupled receptor-targeted antibody candidates