High-Throughput Analysis Identifying Drugs That Regulate Apolipoprotein A-I Synthesis

Assay Drug Dev Technol. 2017 Dec;15(8):362-371. doi: 10.1089/adt.2017.782. Epub 2017 Jul 25.


Apolipoprotein A-I (apo A-I) is the primary antiatherogenic protein in high-density lipoprotein (HDL). Despite the controversy as to the clinical effectiveness of raising HDL, the search is ongoing for safe and effective drugs that increase HDL and apo A-I levels. To identify novel compounds that can increase hepatic apo A-I production, two drug libraries were screened. The NIH clinical collection (NCC) and the NIH clinical collection 2 (NCC2) were purchased from Evotec (San Francisco, CA). The NCC library contains 446 compounds and the NCC2 library contains 281 compounds, all dissolved in dimethylsulfoxide at a concentration of 10 mM. Hepatoma-derived cells (HepG2) and primary hepatocytes in culture were treated with various compounds for 24 h and apo A-I in media samples was measured by enzyme immunoassay. Samples with significant changes in apo A-I concentrations were retested in independent experiments by Western blot analysis to confirm the immunoassay findings. Of a total of 727 compounds screened at a concentration of 50 μM, 15 compounds increased hepatic apo A-I production by 35%-54%, and 9 compounds lowered hepatic apo A-I concentrations in the culture media by 25%-52%. Future trials should explore the clinical effectiveness of these agents when standard doses of these drugs are used in humans.

Keywords: HDL; apolipoproteins; atherosclerosis; gene expression.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apolipoprotein A-I / biosynthesis*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • High-Throughput Screening Assays*
  • Humans
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Apolipoprotein A-I
  • Small Molecule Libraries