HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Telomerase inhibitors identified by a forward chemical genetics approach using a yeast strain with shortened telomere length.

Abstract
Telomerase has been proposed as a selective target for cancer chemotherapy. We established a forward chemical genetics approach using a yeast strain with shortened telomere length. Since this strain rapidly enters cell senescence in the absence of active telomerase, compounds that induce selective growth defects against telomere-shortened yeast could be candidates for drugs acting on telomeres and telomerase. We screened our microbial products library and identified three structurally unrelated antibiotics, chrolactomycin, UCS1025A, and radicicol, as active compounds. Detailed analysis showed that chrolactomycin inhibited human telomerase in a cell-free assay as well as in a cellular assay. Long-term culture of cancer cells with chrolactomycin revealed population-doubling-dependent antiproliferative activity accompanied by telomere shortening. These results suggest that chrolactomycin is a telomerase inhibitor, and that the yeast-based assay is useful for discovering the small molecules acting on human telomerase.
AuthorsRyuichiro Nakai, Hiroyuki Ishida, Akira Asai, Harumi Ogawa, Yoshihiro Yamamoto, Hideki Kawasaki, Shiro Akinaga, Tamio Mizukami, Yoshinori Yamashita
JournalChemistry & biology (Chem Biol) Vol. 13 Issue 2 Pg. 183-90 (Feb 2006) ISSN: 1074-5521 [Print] United States
PMID16492566 (Publication Type: Journal Article)
Chemical References
  • Diterpenes
  • Enzyme Inhibitors
  • chrolactomycin
  • Telomerase
  • beta-Galactosidase
Topics
  • Cell Cycle
  • Cell Line, Tumor
  • Cell-Free System
  • Cellular Senescence
  • Diterpenes (chemistry, pharmacology)
  • Enzyme Inhibitors (chemistry, pharmacology)
  • Humans
  • Saccharomyces cerevisiae (genetics)
  • Telomerase (antagonists & inhibitors)
  • Telomere
  • beta-Galactosidase (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: