Identification of small molecule inhibitors that distinguish between non-transferrin bound iron uptake and transferrin-mediated iron transport

Chem Biol. 2004 Mar;11(3):407-16. doi: 10.1016/j.chembiol.2004.02.016.


Chemical genetics is an emerging field that takes advantage of combinatorial chemical and small molecule libraries to dissect complex biological processes. Here we establish a fluorescence-based assay to screen for inhibitors of iron uptake by mammalian cells. Using this approach, we screened the National Cancer Institute's Diversity Set library for inhibitors of non-transferrin bound iron uptake. This screen identified 10 novel small molecule inhibitors of iron transport with IC(50) values that ranged from 5 to 30 microM. Of these ten compounds, only two blocked uptake of iron mediated by transferrin. Thus, this study characterizes the first small molecule inhibitors that distinguish between different pathways of iron transport.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biological Transport / drug effects
  • Drug Evaluation, Preclinical*
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Iron / metabolism*
  • Molecular Structure
  • Molecular Weight
  • Pharmaceutical Preparations / chemistry
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship
  • Transferrin / antagonists & inhibitors*
  • Transferrin / metabolism*


  • Pharmaceutical Preparations
  • Transferrin
  • Iron