Quinocarmycin analog DX-52-1 inhibits cell migration and targets radixin, disrupting interactions of radixin with actin and CD44

Chem Biol. 2006 Sep;13(9):973-83. doi: 10.1016/j.chembiol.2006.07.011.


In the course of screening for new small-molecule modulators of cell motility, we discovered that quinocarmycin (also known as quinocarcin) analog DX-52-1 is an inhibitor of epithelial cell migration. While it has been assumed that the main target of DX-52-1 is DNA, we identified and confirmed radixin as the relevant molecular target of DX-52-1 in the cell. Radixin is a member of the ezrin/radixin/moesin family of membrane-actin cytoskeleton linker proteins that also participate in signal transduction pathways. DX-52-1 binds specifically and covalently to the C-terminal region of radixin, which contains the domain that interacts with actin filaments. Overexpression of radixin in cells abrogates their sensitivity to DX-52-1's antimigratory activity. Small interfering RNA-mediated silencing of radixin expression reduces the rate of cell migration. Finally, we found that DX-52-1 disrupts radixin's ability to interact with both actin and the cell adhesion molecule CD44.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Biotinylation
  • Cell Line
  • Cell Movement / drug effects*
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Dogs
  • Epithelial Cells / cytology
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Inhibitory Concentration 50
  • Insecta
  • Isoquinolines / chemical synthesis
  • Isoquinolines / metabolism
  • Isoquinolines / pharmacokinetics
  • Isoquinolines / pharmacology
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Protein Binding / drug effects
  • RNA Interference
  • Transfection


  • Actins
  • Cytoskeletal Proteins
  • Hyaluronan Receptors
  • Isoquinolines
  • Membrane Proteins
  • radixin
  • DX 52-1