| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 18, 15566-15572, May 3, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Boehringer Ingelheim Pharma KG, Telomerase, a ribonucleoprotein acting
as a reverse transcriptase, has been identified as a target for cancer
drug discovery. The synthetic, non-nucleosidic compound, BIBR1532, is a
potent and selective telomerase inhibitor capable of inducing
senescence in human cancer cells (1). In the present study, the mode of drug action was characterized. BIBR1532 inhibits the native and recombinant human telomerase, comprising the human telomerase reverse
transcriptase and human telomerase RNA components, with similar
potency primarily by interfering with the processivity of the enzyme.
Enzyme-kinetic experiments show that BIBR1532 is a mixed-type
non-competitive inhibitor and suggest a drug binding site distinct from
the sites for deoxyribonucleotides and the DNA primer, respectively.
Thus, BIBR1532 defines a novel class of telomerase inhibitor with
mechanistic similarities to non-nucleosidic inhibitors of HIV1 reverse transcriptase.
Mechanism of Human Telomerase Inhibition by BIBR1532, a
Synthetic, Non-nucleosidic Drug Candidate*
,,
,, and**
Department
of Oncology Research and ¶ Department of Medicinal Chemistry,
Birkendorfer Strasse 65, 88397 Biberach, Germany, the
§ Swiss Institute for Experimental Cancer Research (ISREC),
CH-1066 Epalinges, Switzerland, and Boehringer Ingelheim Austria
GmbH, Dr. Boehringer Gasse 5-11, A-1120 Vienna, Austria
*
This work was supported in part by the Swiss National
Science Foundation and the Fifth Framework Program of the European
Commission (administered by the Bundesamt fuer Bildung und
Wissenschaft, Bern, Switzerland) (to J. L.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Kelland Targeting the Limitless Replicative Potential of Cancer: The Telomerase/Telomere Pathway Clin. Cancer Res., September 1, 2007; 13(17): 4960 - 4963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M.Y. Wong and K. Collins Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis congenita Genes & Dev., October 15, 2006; 20(20): 2848 - 2858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Ward and C. Autexier Pharmacological Telomerase Inhibition Can Sensitize Drug-Resistant and Drug-Sensitive Cells to Chemotherapeutic Treatment Mol. Pharmacol., September 1, 2005; 68(3): 779 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. El-Daly, M. Kull, S. Zimmermann, M. Pantic, C. F. Waller, and U. M. Martens Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532 Blood, February 15, 2005; 105(4): 1742 - 1749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Crabbe, R. E. Verdun, C. I. Haggblom, and J. Karlseder Defective Telomere Lagging Strand Synthesis in Cells Lacking WRN Helicase Activity Science, December 10, 2004; 306(5703): 1951 - 1953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. AIGNER and T. R. CECH The Euplotes telomerase subunit p43 stimulates enzymatic activity and processivity in vitro RNA, July 1, 2004; 10(7): 1108 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ladetto, M. Compagno, I. Ricca, M. Pagano, A. Rocci, M. Astolfi, D. Drandi, P. F. di Celle, M. Dell'Aquila, B. Mantoan, et al. Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders Blood, June 15, 2004; 103(12): 4644 - 4649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Patry, L. Bouchard, P. Labrecque, D. Gendron, B. Lemieux, J. Toutant, E. Lapointe, R. Wellinger, and B. Chabot Small Interfering RNA-Mediated Reduction in Heterogeneous Nuclear Ribonucleoparticule A1/A2 Proteins Induces Apoptosis in Human Cancer Cells but not in Normal Mortal Cell Lines Cancer Res., November 15, 2003; 63(22): 7679 - 7688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Incles, C. M. Schultes, L. R. Kelland, and S. Neidle Acquired Cellular Resistance to Flavopiridol in a Human Colon Carcinoma Cell Line Involves Up-Regulation of the Telomerase Catalytic Subunit and Telomere Elongation. Sensitivity of Resistant Cells to Combination Treatment with a Telomerase Inhibitor Mol. Pharmacol., November 1, 2003; 64(5): 1101 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Hahn Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer J. Clin. Oncol., May 15, 2003; 21(10): 2034 - 2043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Kim, J. H. Kim, G. E. Lee, J. E. Lee, and I. K. Chung Potent Inhibition of Human Telomerase by Nitrostyrene Derivatives Mol. Pharmacol., May 1, 2003; 63(5): 1117 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Newbold The significance of telomerase activation and cellular immortalization in human cancer Mutagenesis, November 1, 2002; 17(6): 539 - 550. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
