alexa A yeast chemical genetic screen identifies inhibitors of human telomerase.
Molecular Biology

Molecular Biology

Cell & Developmental Biology

Author(s): Wong LH, UncitiBroceta A, Spitzer M, White R, Tyers M,

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Abstract Telomerase comprises a reverse transcriptase and an internal RNA template that maintains telomeres in many eukaryotes, and it is a well-validated cancer target. However, there is a dearth of small molecules with efficacy against human telomerase in vivo. We developed a surrogate yeast high-throughput assay to identify human telomerase inhibitors. The reversibility of growth arrest induced by active human telomerase was assessed against a library of 678 compounds preselected for bioactivity in S. cerevisiae. Four of eight compounds identified reproducibly restored growth to strains expressing active human telomerase, and three of these four compounds also specifically inhibited purified human telomerase in vitro. These compounds represent probes for human telomerase function, and potential entry points for development of lead compounds against telomerase-positive cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.
This article was published in Chem Biol and referenced in Cell & Developmental Biology

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