Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer.
The 3'-ends of human chromosomal DNA terminate in short single-stranded guanine-rich tandem-repeat sequences. In cancer cells, these are associated with the telomere-maintenance enzyme telomerase together with the end-binding protein hPOT1. Small molecules that can compete with these proteins and induce the single-stranded DNA to form quadruplex-ligand complexes are, in effect, able to expose these 3'-ends, which results in the activation of a DNA damage response and selective inhibition of cell growth. Several of these G-quadruplex binding molecules have shown promising anticancer activity in tumour xenograft models, which indicate that the approach may be applicable to the treatment of a wide range of human cancers. This minireview summarizes the available data on these compounds and the challenges posed for drug discovery.
Neidle
Stephen
S
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK. stephen.neidle@pharmacy.ac.uk
D000166:Acridines / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D054856:G-Quadruplexes; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009690:Nucleic Acid Conformation; D016615:Telomere / Q000737:chemistry / Q000187:drug effects
D000166:Acridines; D000970:Antineoplastic Agents; C454064:BRACO-19