Small molecule inhibitors of divalent metal transporter-1

Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G798-804. doi: 10.1152/ajpgi.90342.2008. Epub 2009 Jan 29.

Abstract

Divalent metal transporter-1 (DMT1) is a divalent cation transporter that plays a key role in iron metabolism by mediating ferrous iron uptake across the small intestine. We have previously identified several small molecule inhibitors of iron uptake (4). Using a cell line that stably overexpresses DMT1, we screened the ability of these inhibitors to specifically block this transporter's activity. One compound, NSC306711, inhibited DMT1-mediated iron uptake in a reversible and competitive manner. This inhibitor is a polysulfonated dye containing two copper centers. Although one of these two sites could be chelated by Triethylenetetramine copper chelation did not perturb NSC306711 inhibition of DMT1 activity. Several other polysulfonated dyes with structural features similar to NSC306711 were identified as potential DMT1 transport inhibitors. This study characterizes important pharmacological tools that can be used to probe DMT1's mechanism of iron transport and its role in iron metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cation Transport Proteins / antagonists & inhibitors*
  • Cation Transport Proteins / metabolism*
  • Cell Line
  • Humans
  • Iron Radioisotopes / metabolism
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Cation Transport Proteins
  • Iron Radioisotopes
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2