Document Type



Life Sciences | Medicine and Health Sciences


Telomerase is a reverse transcriptase that maintains telomere length. Telomerase activity is suppressed in somatic cells such that telomere attrition triggers replicative senescence or apop-tosis. In cancer cells, telomerase is up-regulated or reactivated, effectively making the cell immortal. Previous studies have shown that telomerase activity positively correlates with unfavorable cancer prognosis. Since it was discovered that activation of telomerase is a rate-limiting step in carcinogenesis, telomerase has gained much interest as a drug target. Both screening and structure-based methods have been extensively employed to identify small molecule leads that can selectively disrupt telomerase activity. Strategies commonly used to target telomerase activity include but are not limited to targeting the reverse transcriptase subunit of telomerase (BIBR1532 and nucleoside ananlogs), inhibiting hTERT phosphorylation using inhibitors of protein kinase C, targeting the RNA component of telomerase (peptide nucleic acids, antisense oligonucleotides - GRN163L), stabilizing G-quaduplex structures, and using T-oligos that mimic the end of human telomeres to induce a DNA-damage response. Nonetheless, with the exception of GRN163L that has recently entered into Phase III clinical trials, attempts at clinically targeting telomerase activity using classic small molecule derivatives have largely been unsuccessful.


Chembiochem. Author manuscript; available in PMC 2014 May 20. Published in final edited form as: Chembiochem. 2013 March 4; 14(4): 445–451. doi:10.1002/cbic.201200777