Wheeler J, Tanglao S, Karakas B, Lovell T, Brown LK, Tersteege L, Andrews WH, Burke P, Pawlik O, Zhang J, Mohammadpour H, Briggs LA.

Telomerase is of significant interest to many scientists for its ability to immortalize cells, usually expressed in most tumor cells and human embryonic stem cells, but it is silenced in normal differentiated cells. Cancer researchers are focused on the inhibition of telomerase activity in cancer cells for therapeutic purposes while anti-aging enthusiasts are interested in de-repressing telomerase expression. Induction of telomerase activity could contribute to maintaining telomere length and elongation of telomeres in normal somatic cells thus possibly extending replicative life span. Introducing a drug to cells that could potentially control the induction of telomerase would be a medical breakthrough in the cure for many age-related diseases.

C0057684 was discovered in a high throughput transient hTERT promoter-reporter expression system. Further research showed that cells exposed to C0057684 resulted in the expression of endogenous hTERT. This confirmation led to testing the compound's ability to induce telomerase in various cell lines by measuring hTERT mRNA by RT-PCR and telomerase enzyme activity through TRAP assays. C0057684 has been tested in normal somatic cells, ALT cell lines and telomerase positive cells. After compound exposure all normal cell lines have shown induced telomerase activity, indicating the de-repression of the telomerase promoter. In addition to our current research we are testing analogs of C0057684 and non-analogs, studying the extension of replicative life span, conducting toxicity experiments, and various additional studies.