Medicinal chemistry and actions of dual and pan PPAR modulators

Ernest Adeghate, Abdu Adem, Mohamed Y. Hasan, Kornelia Tekes, Huba Kalasz

Research output: Contribution to journalReview articlepeer-review

46 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor (PPAR) agonists are used as adjunct therapy in the treatment of diabetes mellitus. Fibrates, including fenofibrate, gemfibrozil, benzafibrate, ciprofibrate, and clofibrate act on PPAR alpha to reduce the level of hypertriglyceridemia. However, agonists (ligands) of PPAR-beta/delta receptors, such as tesaglitazar, muraglitazar, ragaglitazar, imiglitazar, aleglitazar, alter the body's energy substrate preference from glucose to lipids and hence contribute to the reduction of blood glucose level. Glitazones or thiazolidinediones on the other hand, bind to PPAR-gamma receptors located in the nuclei of cells. Activation of PPAR-gamma receptors leads to a decrease in insulin resistance and modification of adipocyte metabolism. They reduce hyperlipidaemia by increasing the level of ATPbinding cassette A1, which modifies extra-hepatic cholesterol into HDL. Dual or pan PPAR ligands stimulate two or more isoforms of PPAR and thereby reduce insulin resistance and prevent short- and long-term complications of diabetes including micro-and macroangiopathy and atherosclerosis, which are caused by deposition of cholesterol. This review examines the chemical structure, actions, side effects and future prospects of dual and pan PPAR agonists.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalOpen Medicinal Chemistry Journal
Volume5
Issue numberSPEC. ISSUE 2
DOIs
Publication statusPublished - 2011

Keywords

  • Diabetes mellitus
  • Fibrates
  • Medicinal chemistry
  • PPAR agonists
  • Thiazolidinediones

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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