Medicinal chemistry and actions of dual and pan PPAR modulators

Ernest Adeghate, Abdu Adem, Mohamed Y. Hasan, K. Tekes, H. Kalász

Research output: Contribution to journalArticle

39 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

Fingerprint

Peroxisome Proliferator-Activated Receptors
Pharmaceutical Chemistry
Thiazolidinediones
PPAR gamma
Insulin Resistance
PPAR delta
Gemfibrozil
Ligands
Fenofibrate
Pharmacologic Actions
Fibric Acids
Clofibrate
PPAR alpha
delta Opioid Receptor
Hypertriglyceridemia
Diabetes Complications
Hyperlipidemias
Cell Nucleus
Adipocytes
HDL Cholesterol

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Medicinal chemistry and actions of dual and pan PPAR modulators. / Adeghate, Ernest; Adem, Abdu; Hasan, Mohamed Y.; Tekes, K.; Kalász, H.

In: Open Medicinal Chemistry Journal, Vol. 5, No. SPEC. ISSUE 2, 2011, p. 93-98.

Research output: Contribution to journalArticle

Adeghate, Ernest ; Adem, Abdu ; Hasan, Mohamed Y. ; Tekes, K. ; Kalász, H. / Medicinal chemistry and actions of dual and pan PPAR modulators. In: Open Medicinal Chemistry Journal. 2011 ; Vol. 5, No. SPEC. ISSUE 2. pp. 93-98.
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