Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI

Thomas J F Nieland, Jared T. Shaw, Firoz A. Jaipuri, Zoltan Maliga, Jay L. Duffner, Angela N. Koehler, Monty Krieger

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Treatment of atherosclerotic disease often focuses on reducing plasma LDL-cholesterol or increasing plasma HDL-cholesterol. We examined in vitro the effects on HDL receptor [scavenger receptor class B type I (SR-BI)] activity of three classes of clinical and experimental plasma HDL-cholesterol-elevating compounds: niacin, fibrates, and HDL376. Fenofibrate (FF) and HDL376 were potent (IC50 ∼ 1 μM), direct inhibitors of SR-BI-mediated lipid transport in cells and in liposomes reconstituted with purified SR-BI. FF, a prodrug, was a more potent inhibitor of SR-BI than an activator of peroxisome proliferator-activated receptor a, a target of its active fenofibric acid (FFA) derivative. Nevertheless, FFA, four other fibrates (clofibrate, gemfibrozil, ciprofibrate, and bezafibrate), and niacin had little, if any, effect on SR-BI, suggesting that they do not directly target SR-BI in vivo. However, similarities of HDL376 treatment and SR-BI gene knockout on HDL metabolism in vivo (increased HDL-cholesterol and HDL particle sizes) and structure-activity relationship analysis suggest that SR-BI may be a target of HDL376 in vivo. HDL376 and other inhibitors may help elucidate SR-BI function in diverse mammalian models and determine the therapeutic potential of SR-BI-directed pharmaceuticals.

Original languageEnglish (US)
Pages (from-to)1832-1845
Number of pages14
JournalJournal of Lipid Research
Issue number8
StatePublished - Aug 2007
Externally publishedYes


  • Fenofibrate
  • Fibrates
  • HDL376
  • High density lipoprotein
  • Lipoprotein metabolism
  • Niacin
  • Scavenger receptor class B type I
  • Structure-activity relationship

ASJC Scopus subject areas

  • Endocrinology


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