Drug targeting of the c-MYC promoter to repress gene expression via a G-quadruplex silencer element

Semin Oncol. 2006 Aug;33(4):498-512. doi: 10.1053/j.seminoncol.2006.04.012.


In this review, we describe the evidence for a parallel-stranded G-quadruplex in the purine-rich strand of the nuclease hypersensitivity element III(1) (NHE III(1)) of the promoter of c-MYC upstream of the P1 and P2 promoters. This biologically relevant G-quadruplex is a mixture of four loop isomers. The folding pattern of a nuclear magnetic resonance (NMR)-derived structure for the predominant loop isomer of this G-quadruplex has been obtained. This G-quadruplex has been demonstrated to be a silencer element, and the cationic porphyrin TMPyP4 has been shown to stabilize this G-quadruplex. Furthermore, TMPyP4 has been shown to repress c-MYC expression, and this effect is mediated through the silencer element. Last, the in vivo activity of TMPyP4 in xenograph models is presented.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Gene Silencing
  • Genes, myc / drug effects*
  • Humans
  • Isomerism
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Silencer Elements, Transcriptional
  • Transcription, Genetic


  • Porphyrins
  • Proto-Oncogene Proteins c-myc
  • tetra(4-N-methylpyridyl)porphine