title: Discovery Approaches for Novel Dyslipidemia Drugs.
abstract: BACKGROUND
  Dyslipidemia is increased fasting level of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG), along with decreased levels of HDL cholesterol (HDL-C). Owing to effect on the cardiovascular system and increased chances of metabolic diseases, it is needed to review novel under development drugs and new approaches in drug discovery for dyslipidemia.
  
  
  METHODS
  This article reviews all phases I to IV clinical trials and preclinical trials with results associated with novel treatment of dyslipidemia. Drug discovery for dyslipidemia, toward newer targets has been addressed.
  
  
  RESULTS
  Statins are, currently available, best choice of drugs for treating dyslipidemia and coronary diseases. In addition to this, lipid lowering drugs support treatment to a great extent, either as monotherapy or in combinations with other groups. Pravastatin used in combination with cholesteryl ester, transfers protein inhibitors (CETP) to produce efficient results. Peroxisome proliferator-activated receptor agonists (PPAR) like muraglitazar, aleglitazar and tesaglitazar are PPAR α/γ receptor agonist, dual in action performs better in phase 3 clinical study and reduces renal and cardiovascular events. By targeting both receptors, a better treatment for cardiovascular and diabetic problems can be achieved. Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors like humanized monoclonal antibodies, are newly discovered inhibitors that reduce the risk of cardiovascular diseases. During the past few years, nucleic acid-based therapies targeting lipid and lipoprotein metabolism, such as microsomal TG transfer protein (MTP) may be a promising therapeutic approach to treat vascular diseases. Gene regulating transcription factors involved in bile acids and cholesterol metabolism can be controlled by FXR agonists in dyslipidemia. To overcome these drawbacks, many thyroid hormone analogues have been developed to lower down cholesterol level by targeting specifically thyroid hormone β receptors abundantly present in the liver without severe side effects. Virtual screening, an important tool in screening databases of the lead compounds, provides a good platform to access new compounds. In this review, examples of novel FXR modulators, thyromimetic agents, cholesterol absorption inhibitors and other new anti hyperlipidemia scaffolds have been addressed.
authors.forename: Faheem
authors.initials: F
authors.lastname: Maqbool
authors.forename: Malihe
authors.initials: M
authors.lastname: Safavi
authors.forename: Haji
authors.initials: H
authors.lastname: Bahadar
authors.forename: Mahban
authors.initials: M
authors.lastname: Rahimifard
authors.forename: Kamal
authors.initials: K
authors.lastname: Niaz
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran, University of Medical Sciences, Tehran, Iran. Mohammad.Abdollahi@UToronto.Ca.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D035703:Therapies, Investigational; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D014280:Triglycerides; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases