title: G Protein-Coupled Receptor 119 (GPR119) Agonists for the Treatment of Diabetes: Recent Progress and Prevailing Challenges.
abstract: In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in the search for GPR119 agonists, making it a highly competitive area in the industrial environment. Several GPR119 agonists have been entered into clinical studies, but many have failed either in phase I or II and none has progressed beyond phase II. Herein we describe the strategies chosen by the different medicinal chemistry teams in academia and the pharmaceutical industry to improve potency, physicochemical properties, pharmacokinetics, and the safety profile of GPR119 agonists in the discovery phase in order to improve the odds for successful development.
authors.affiliation: Sanofi-Aventis Deutschland GmbH , Building G838, Industriepark Hoechst, 65926 Frankfurt, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Ritter
authors.affiliation: Sanofi-Aventis Deutschland GmbH , Building G838, Industriepark Hoechst, 65926 Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Buning
authors.affiliation: Sanofi-Aventis Deutschland GmbH , Building G838, Industriepark Hoechst, 65926 Frankfurt, Germany.
authors.forename: Nis
authors.initials: N
authors.lastname: Halland
authors.affiliation: Sanofi-Aventis Deutschland GmbH , Building G838, Industriepark Hoechst, 65926 Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pöverlein
authors.affiliation: Sanofi-Aventis Deutschland GmbH , Building G838, Industriepark Hoechst, 65926 Frankfurt, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Schwink
mesh_terms: D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy*; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism
chemical_list: C519854:GPR119 protein, human; D008024:Ligands; D043562:Receptors, G-Protein-Coupled