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.