title: PPAR agonists, - Could tissue targeting pave the way?
abstract: Over the last couple of decades, the PPAR family of transcription factors has received much attention from the pharmaceutical industry due to their profound ability to improve glucose and lipid metabolism upon agonist activation. However, more recently the interest in these nuclear receptors has faded because several clinical trials have shown that it is difficult to develop a ligand that significantly ameliorates glucose and lipid metabolism disorders without concomitantly inducing unacceptable side-effects. Nevertheless, the data also suggests that tissue specific targeting could pave the way to renewed interest and clinical use of PPAR ligands. In this review we summarize the results and learnings from the clinical trials on PPAR agonism and discuss the possibilities for tissue targeting of PPAR ligands by using state of the art technology to fuse them to peptides homing selectively to tissues expressing the cognate surface receptor.
authors.affiliation: Department of Obesity Biology, Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Bugge
authors.affiliation: Department of Obesity Biology, Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark. Electronic address: Doho@novonordisk.com.
authors.forename: Dorte
authors.initials: D
authors.lastname: Holst
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones
keywords: Clinical outcome; PPAR agonism; Tissue specific targeting