Effects of F-1394, an Acyl-CoA:Cholesterol Acyltransferase (ACAT) Inhibitor, on ACAT Activity in HepG2 Cells and on Hepatic Secretion of Lipids in Triton WR-1339-Induced Hyperlipidemic Rats: Possible Role of Hepatic ACAT in Very Low Density Lipoprotein Secretion

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Author(s)

Abstract

We examined the inhibitory potency of F-1394 ((1<I>S</I>, 2<I>S</I>)-2-[3-(2, 2-dimethylpropyl)-3-nonylureido]cyclohexane-1-yl 3-[(4<I>R</I>)-<I>N</I>-(2, 2, 5, 5-tetramethyl-1, 3-dioxane-4-carbonyl)amino]propionate), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on ACAT activity and its hypolipidemic effect. F-1394 inhibited whole-cell ACAT activity in HepG2 cells with an IC<SUB>50</SUB> value of 42 nM. The potency of F-1394 was greater than that of the five other ACAT inhibitors tested (YM-17E, CI-976, 57-118, CL-277, 082 and DL-melinamide). In rats made hyperlipidemic by Triton WR-1339, F-1394 caused a reduction in the hepatic secretion rate of cholesterol. These data suggest that inhibition of hepatic ACAT activity helps to reduce very low density lipoprotein secretion from the liver into the circulation.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 76(3), 309-312, 1998-03

    The Japanese Pharmacological Society

References:  15

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008192108
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4440451
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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