Unlimited cellular proliferation of cancer cells is coupled with the maintenance of telomeres in DNA. Telomerase, the enzyme that re-extends telomeres, has become an attractive target for new cancer therapeutics. BIBR1532, a mixed-type non-competitive inhibitor of telomerase, has been shown to cause growth arrest in tumor cells. Here, we tested BIBR1532 and five synthetic analogues (WS6-48, WS4-43A, WS5-29, WS7-6, WS8-3) for anti-proliferative activity on metastatic prostate cancer cells. Preliminary results indicate these compounds are highly active against proliferation. Their effects on inhibiting telomerase activity directly were quantified using a telomere repeat amplification protocol assay. Newly developed analogues are under preliminary testing to determine their effect upon telomerase. Available x-ray structures of telomerase domains are also being explored to asses putative binding sites and affinities. Further studies will assess the effect these compounds have on other metastatic cancer cell lines.
Rogers, Thomas; Chowdhary, Anirudh; Szarecka, Agnieszka; Schroeder, William; Smart, Robert; and Sridhar, Suganthi, "Investigating the Effects of BIBR1532 and Related Analogs on Telomerase Activity in Human Prostate Cancer Cells" (2012). Honors Projects. Paper 161.