title: Early investigational drugs targeting PPAR-α for the treatment of metabolic disease.
abstract: BACKGROUND
  The fibrates have been used for many years to treat dyslipidemias and have also recently been shown to have anti-inflammatory effects. They are relatively weak PPAR-α agonists and do have some adverse effects. Novel compounds are in development, which are selective PPAR modulators (SPPARMs) and have more potent PPAR-α agonist activity. These may prove to have advantages in the treatment of dyslipidemia, insulin resistance and non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  This review focuses on PPAR-α agonists or SPPARMs in development describing the preclinical and early clinical studies. The information was obtained by searching the published literature and abstracts from recent meetings. Ongoing clinical trials were identified using the Clinicaltrial.gov database.
  
  
  CONCLUSIONS
  There is still a need for new drugs to treat atherogenic dyslipidemia. The highly potent and selective PPAR-α agonist K-877 has shown beneficial effects on atherogenic dyslipidemia and absence of some adverse effects seen with fibrates. The dual PPAR-α/PPAR-δ agonist GFT-505 has shown favorable results in improving atherogenic dyslipidemia and insulin resistance and appears to be a potential candidate for the treatment of NAFLD. Long-term trials are needed to assess the safety and efficacy of these new agents for cardiovascular and liver outcomes.
authors.affiliation: Tongji University, Shanghai East Hospital, Department of Cardiac Surgery , No 150, Jimo Road, Shanghai 200120 , China liu.zhongmin@tongji.edu.cn.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Liu
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002087:Butyrates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D047188:Chalcones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000503:physiopathology; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists; D011422:Propionates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C585906:2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid; D001583:Benzoxazoles; D002087:Butyrates; D047188:Chalcones; D015507:Drugs, Investigational; C000603947:K-877 compound; D047493:PPAR alpha; D047495:PPAR gamma; D011422:Propionates
keywords: GFT-505; K-877; PPAR-α agonists; atherogenic dyslipidemia; fenofibrate