IMB2026791, a xanthone, stimulates cholesterol efflux by increasing the binding of apolipoprotein A-I to ATP-binding cassette transporter A1

Molecules. 2012 Mar 7;17(3):2833-54. doi: 10.3390/molecules17032833.


It is known that the ATP-binding cassette transporter A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I) will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS) method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO) cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein) expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791) was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell) further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC(50) of 25.23 μM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / agonists
  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Apolipoprotein A-I / metabolism*
  • CHO Cells
  • Cell Survival / drug effects
  • Cholesterol / metabolism*
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Glyburide / pharmacology
  • Green Fluorescent Proteins / metabolism
  • High-Throughput Screening Assays
  • Humans
  • Inhibitory Concentration 50
  • Protein Binding
  • Recombinant Fusion Proteins / agonists
  • Recombinant Fusion Proteins / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Xanthones / pharmacology*


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoprotein A-I
  • IMB2026791
  • Recombinant Fusion Proteins
  • Xanthones
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Cholesterol
  • Tetradecanoylphorbol Acetate
  • Glyburide