Structural features of subtype-selective EP receptor modulators

•PGE2 receptor subtypes EP1-4 are valuable drug targets.•Structural features for subtype-selective activity of EP1-4 receptor modulators are presented.•Binding affinities, functional activities and selectivities of presented EP modulators are provided.•Recent findings of the clinical value of EP receptor modulators are discussed.

Prostaglandin E2 is a potent endogenous molecule that binds to four different G-protein-coupled receptors: EP1-4. Each of these receptors is a valuable drug target, with distinct tissue localisation and signalling pathways. We review the structural features of EP modulators required for subtype-selective activity, as well as the structural requirements for improved pharmacokinetic parameters. Novel EP receptor subtype selective agonists and antagonists appear to be valuable drug candidates in the therapy of many pathophysiological states, including ulcerative colitis, glaucoma, bone healing, B cell lymphoma, neurological diseases, among others, which have been studied in vitro, in vivo and in early phase clinical trials.

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