Tanglao S, Wheeler J, Karakas B, Graham J, Zhang J, Brown LK, Tersteege L, Andrews WH, Burke P, Foster CA, Mohammadpour H, Briggs LA, Gaeta F, Piatyszek MA, Kerley T.

The long term goal of Sierra Sciences LLC is to find a compound that induces telomerase activity for basic research purposes as well as anti-aging therapeutic applications. As a result of our cell-based high throughput screening effort utilizing a transient hTERT minimal promoter and luciferase reporter expression system, 929 compounds from a diversified small molecule library of over 123,840 compounds were found to induce luciferase expression. Cells treated with the active compounds from our primary screen are being examined for hTERT mRNA expression through real-time RT-PCR. While approximately 80% of these active compounds are still under evaluation in cell-based assays, we have identified C0057684 as an inducer of mRNA expression in several cell lines. Furthermore, C0057684 treated cells were evaluated for telomerase enzyme activity through the Telomere Repeat Amplification Protocol (TRAP). In a series of such studies, C0057684 was able to consistently induce telomerase activity. Further investigation of C0057684, analogs, and its pharmacophore are currently in progress at Sierra Sciences.