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Identification of a series of potent telomerase inhibitors using a time‐resolved fluorescence‐based assay
Author(s) -
Bare Lance A.,
Trinh Lan,
Wu Shung,
Devlin James J.
Publication year - 1998
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199802)43:2<109::aid-ddr4>3.0.co;2-o
Subject(s) - telomerase , chemistry , oligonucleotide , high throughput screening , taq polymerase , microbiology and biotechnology , fluorescence , chromatography , polymerase , biochemistry , dna , biology , thermus aquaticus , physics , quantum mechanics , gene
A high‐throughput, nonradioactive telomerase assay using a europium‐labeled oligonucleotide probe and time‐resolved fluorescence has been developed to detect PCR‐amplified telomerase products. The use of a thermally activated TAQ polymerase, rather than a wax barrier, to implement a PCR hot‐start facilitated the use of laboratory automation equipment. Results obtained with this high‐throughput protocol correlate well with those obtained with the TRAP protocol. Screening a set of 125,000 compounds from the Berlex library, we identified a set of isothiazolone‐containing telomerase inhibitors. The most potent of these inhibitors have submicromolar IC 50 values and may be reacting with a telomerase thiol. These compounds may be useful tools to evaluate the effects of telomerase in cancer cells. Drug Dev. Res. 43:109–116, 1998. © 1998 Wiley‐Liss, Inc.