Oligonucleotide conjugate GRN163L targeting human telomerase as potential anticancer and antimetastatic agent

Nucleosides Nucleotides Nucleic Acids. 2007;26(10-12):1577-9. doi: 10.1080/15257770701547271.

Abstract

Telomerase is one of the key enzymes responsible for the proliferative immortality of the majority of cancer cells. We recently introduced a new telomerase inhibitor, a 13-mer oligonucleotide N3' --> P5'-thio-phosphoramidate lipid conjugate, designated as GRN163L. This compound inhibits telomerase activity in various tumor cell lines with IC(50) values of 3-300 nM without any cellular uptake enhancers. GRN163L demonstrated potent and sequence specific anti-cancer activity in vivo in multiple animal models. This compound was able to significantly affect not only the growth of primary tumors, but also the spread and proliferation of metastases. GRN163L is currently in Phase I and Phase I/II clinical studies in patients with solid tumors and CLL, respectively.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Mice
  • Oligonucleotides
  • Oligopeptides / pharmacology*
  • Oligopeptides / therapeutic use
  • Telomerase / antagonists & inhibitors*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • GRN163L peptide
  • Oligonucleotides
  • Oligopeptides
  • Telomerase