Inhibitor SourceBook™ Second Edition

Cell Division/Cell Cycle/Cell Adhesion
Telomerase Inhibitors
Telomerase is a specialized ribonucleoprotein composed
of a catalytic subunit telomerase reverse transcriptase
(TERT), and two other subunits known as telomerase
associated protein 1 (TP1), and a ~445-nucleotide long
telomerase RNA component (TR). Telomerase stabilizes
telomere lengths by adding hexameric (TTAGGG) repeats
to the ends of chromosomes, thereby circumventing
the cumulative damage that normally occurs during
mitotic cell division. Telomerase recognizes the G-rich
strand of an existing telomere repeat sequence and
elongates it in the 5´-to-3´ direction. Progressive loss of
telomeres, a key feature of normal cells, is considered to
be a major regulator of cellular senescence. Tumor cells
overcome this problem by overexpressing telomerase.
As cancer cells divide more often, on an average, they
possess shorter telomeres than normal cells. Hence,
without an active telomerase to maintain telomere
length, cancer cells could reach critically short telomere
at a faster pace than normal cells. Telomerase activity,
which is practically undetectable in normal cells, is
detected in the majority of tumor cells. The presence
of telomerase activity is correlated with poor clinical
outcome in cancer patients. Hence, telomerase inhibitors
Telomerase Inhibitors
are considered as potential therapeutic agents for the
management of tumor progression.
Promising approaches for telomerase inhibition include
the use of mutant dominant/negative versions of human
TERT (hTERT) and the use of antisense oligonucleotides
directed against the template RNA component (hTR) of
the telomerase holoenzyme. These telomerase inhibitors
reduce telomerase activity and lead to progressive
shortening of telomeres with each cell division,
ultimately causing cells to undergo apoptosis.
References:
Altshuler, M.L., et al. 2003. Biochemistry (Mosc). 68, 275.
Mokbel, K. 2003. Curr. Med. Res. Opin. 19, 470.
Wu, X., et al. 2003. J. Natl. Cancer Inst. 95, 2 .
Gomez, D., et al. 2002. Cancer Res. 62, 3365.
Shay, J.W., et al. 200 . Hum. Mol. Gen. 10, 677.
Rahat, M.A., et al. 999. Cancer 85, 9 9.
Roos, G., et al. 998. Int. J. Cancer 79, 343.
Wen, J., et al. 998. Mol. Diagn. 3, 29.
Kim, N.W. 997. Eur. J. Cancer 33, 78 .
Shay, J.W. 997. J. Cell. Physiol. 173, 266.
Harrington, L., et al. 997. Science 275, 973.
Product Cat. No. Comments Size Price
3´-Azido-3´-
deoxythymidine
InSolution AZT,
Triphosphate,
Tetralithium Salt
3´-Deoxy-2´,3´-
didehydrothymidine
Ellipticine, 9-Hydroxy-,
Hydrochloride
(–)-Epigallocatechin
Gallate
More online... www.calbiochem.com/inhibitors/telomerase
194348 (AZT)
Inhibitor of HIV- reverse transcriptase that blocks the incorporation of
nucleotides into newly synthesized DNA. Causes irreversible telomere shortening.
194950 (AZTTP)
A reverse transcriptase inhibitor that acts by docking to the active site of HIVreverse
transcriptase. Also reported to inhibit telomerase activity in vitro
(IC 50 = 30 mM).
257920 A reverse transcriptase inhibitor that causes a consistent and rapid telomere
shortening in vegetatively growing Tetrahymena.
324680 (9-HE, HCl)
An antitumor alkaloid that is reported to inhibit telomerase activity in cultured
pancreatic cancer cells, in a time- and concentration-dependent manner,
possibly through inhibition of protein kinases. It also acts as a potent inhibitor of
topoisomerase II (IC 50 = 3.3 mM).
324880 {EGCG; (2R,3R)-2-(3,4,5-Trihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7triol-3-(3,4,5-trihydroxybenzoate)}
A polyphenolic constituent of green tea with potent antitumor, anti-inflammatory,
and antioxidant properties. Strongly and directly inhibits telomerase activity in
cell-free systems and in cancer cell lines.
PIPER 528120 {N,N´-bis[2-(1-Piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic Diimide; Telomerase
Inhibitor IV}
A perylene-based ligand that potently inhibits human telomerase activity by
binding to G-quadruplex DNA. The strongest binding site for PIPER appears to be
the 3'-boundary of the G-quadruplex. Can also bind non-specifically to nucleic
acids.
0 mg $39
mmol $ 60
25 mg $76
0 mg $55
0 mg $39
0 mg $85
80 Orders Phone 800 854 34 7
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