Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints

Current Medicinal Chemistry. Anti-cancer Agents
Yves Pommier

Abstract

Camptothecins selectively target topoisomerase I (Top1) by trapping the catalytic intermediate of the Top1-DNA reaction, the cleavage complex. Hence, camptothecins represent a paradigm for targeting macromolecular interactions. Instead of preventing the binding of the two macromolecules they target (Top1 and DNA), camptothecins slow down the dissociation of these macromolecules. The activity of camptothecins underlines the usefulness of screening for drugs that inhibit the dissociation of macromolecules. Camptothecins and non-CPT Top1 inhibitors are being developed to improve the pharmacodynamics, pharmacokinetics and clinical pharmacology of camptothecins, and it is likely that drugs with improved anticancer activity will be discovered. Although Top1 is the only primary target of camptothecins, the mechanisms of camptothecins' anticancer activity rest beyond the formation of cleavage complexes. Indeed, Top1 cleavage complexes lead to replication- (and transcription-) mediated DNA damage. It is likely that DNA damage can be repaired more efficiently in normal than in cancer cells that are intrinsically deficient for DNA repair and cell cycle checkpoints. Evaluating such deficiencies in clinical samples is becoming possible. If ...Continue Reading

Citations

Jun 26, 2010·The Journal of Biological Chemistry·Seong Jun Cho, Xinbin Chen
Aug 21, 2012·Antioxidants & Redox Signaling·V Ashutosh Rao
Jun 20, 2006·Molecular and Cellular Biology·Robert C A M van WaardenburgMary-Ann Bjornsti
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·T K Li, L F Liu
Apr 23, 2009·Molecular Cancer Therapeutics·Yves Pommier, Mark Cushman
Feb 20, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gerhard HamiltonTheresia Thalhammer
Oct 6, 2009·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Paul J SmithRachel J Errington
Sep 13, 2006·Biochemical Pharmacology·Yvette Habraken, Jacques Piette
Jun 8, 2006·Biochimica Et Biophysica Acta·R M RegueraR Balaña-Fouce
Sep 24, 2013·Investigational New Drugs·Cheree FitzgibbonChristopher Bradley
Apr 27, 2005·Archives of Biochemistry and Biophysics·Man Sup KwackJung Sup Lee
May 17, 2012·Biochimica Et Biophysica Acta·Xiukun CuiMugen Liu
Oct 26, 2010·Biochimica Et Biophysica Acta·Shi-Hong MaPaul B S Lai
Aug 10, 2006·Annual Review of Genetics·Claire Wyman, Roland Kanaar
Aug 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Supipi DuffyPhilip Hieter
Sep 17, 2016·Nature Communications·Valentina PalermoPietro Pichierri
Jun 24, 2017·Environmental Science and Pollution Research International·Zhi ZhangShide Liu
Apr 2, 2008·Genes & Genetic Systems·Tomoko HayashiTakemi Enomoto
Sep 2, 2008·Nature Reviews. Drug Discovery·Mark E DavisDong M Shin
Feb 2, 2011·Nature Reviews. Clinical Oncology·Edina Komlodi-PasztorTito Fojo
Aug 12, 2014·World Journal of Gastroenterology : WJG·Mariusz Panczyk
May 19, 2018·Current Medicinal Chemistry·Rosa M RegueraRafael Balaña-Fouce
Mar 3, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Muthu K KathiravanKishor S Jain
Apr 7, 2005·The Journal of Biological Chemistry·Amy C RaymondAlex B Burgin
Feb 19, 2020·Anti-cancer Agents in Medicinal Chemistry·Yeliz DemirŞükrü Beydemir
Jul 13, 2007·The Journal of Biological Chemistry·Shmuel CohenMichael A Firer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Related Papers

The Journal of Biological Chemistry
Héctor VillaDavid Ordóñez
Proceedings of the National Academy of Sciences of the United States of America
A L BodleyT A Shapiro
© 2021 Meta ULC. All rights reserved