Topoisomerase I inhibitors: camptothecins and beyond

@article{Pommier2006TopoisomeraseII,
  title={Topoisomerase I inhibitors: camptothecins and beyond},
  author={Yves Pommier},
  journal={Nature Reviews Cancer},
  year={2006},
  volume={6},
  pages={789-802}
}
  • Y. Pommier
  • Published 1 October 2006
  • Biology, Medicine
  • Nature Reviews Cancer
Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme. It is the only known target of the alkaloid camptothecin, from which the potent anticancer agents irinotecan and topotecan are derived. As camptothecins bind at the interface of the TOP1–DNA complex, they represent a paradigm for interfacial inhibitors that reversibly trap macromolecular complexes. Several camptothecin and non-camptothecin derivatives are being developed to further increase anti-tumour activity and reduce side… Expand
Tyrosyl-DNA Phosphodiesterase 1 Inhibitors: Usnic Acid Enamines Enhance the Cytotoxic Effect of Camptothecin.
TLDR
These new compounds enhanced the cytotoxicity of the established Top1 poison camptothecin by an order of magnitude. Expand
Targeting topoisomerase I: molecular mechanisms and cellular determinants of response to topoisomerase I inhibitors
TLDR
This review provides an overview of the recent achievements in the development of topoisomerase I inhibitors and in the explanation of the biological pathways involved in tumor response and suggests a growing body of evidence supports the possibility of optimizing the therapeutic profile of available agents. Expand
Recent developments in topoisomerase-targeted cancer chemotherapy
TLDR
The focus of this review will be to summarize the current state of the art with respect to clinically used topoisomerase inhibitors for targeted cancer treatment and to discuss the pharmacology and chemistry of promising new topoisomersase inhibitors in clinical and pre-clinical development. Expand
Dual DNA topoisomerase 1 and tyrosyl‐DNA phosphodiesterase 1 inhibition for improved anticancer activity
TLDR
Findings from studies reporting the combined inhibition of Top1 and Tdp1 are summarized to highlight the importance of knowing which approaches are considered for developing drug precursors for cancer drug design. Expand
DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
TLDR
This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors and discusses the common mechanism of action ofTopoisomerase poisons by interfacial inhibition and trapping of topisomerase cleavage complexes. Expand
A computational molecular docking study of camptothecin similars as inhibitors for topoisomerase 1
DNA topoisomerase 1 (Top1) is a prime target of chemotherapy agents and a crucial enzyme that maintains DNA topology, during transcription, replication, repair, and recombination by relaxing DNAExpand
Next generation topoisomerase I inhibitors: Rationale and biomarker strategies.
  • B. Teicher
  • Biology, Medicine
  • Biochemical pharmacology
  • 2008
TLDR
Biomarkers are under investigation to predict clinical efficacy from preclinical models, to allow determination of drug targeting in vivo and to aid selection of patients most likely to benefit from TopoI inhibitor therapy. Expand
Topoisomerase I Inhibitors: Chemical Biology
Topoisomerase I (Top1), an essential enzyme, produces a DNA single-strand break allowing DNA relaxation for replication. The enzymatic mechanism involves sequential transesterifications and theExpand
DNA cleavage assay for the identification of topoisomerase I inhibitors
TLDR
One of the most frequently used protocols to identify novel Top1 inhibitors is described, which provides a suitable system for determining whether the inhibitor blocks the forward cleavage or religation reactions by measuring the reversibility of the drug-induced Top1–DNA cleavage complexes. Expand
Effective Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 Based on Monoterpenoids as Potential Agents for Antitumor Therapy
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the important DNA repair enzymes responsible for the repair of DNA damage caused by anticancer drugs, such as topotecan. In this regard, enzymeExpand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 169 REFERENCES
Non-camptothecin DNA topoisomerase I inhibitors in cancer therapy.
TLDR
Among the non-camptothecin inhibitors, the indolocarbazoles are the most advanced in their development, and are in clinical trials and the potential binding site(s) of topoisomerase I inhibitors in the enzyme I-DNA complex is discussed. Expand
Topoisomerase I inhibitors: selectivity and cellular resistance.
Topoisomerase I (top1) inhibitors (camptothecins and other structurally diverse compounds) are effective and promising anticancer agents. Determinants of selectivity toward cancer cells andExpand
The mechanism of topoisomerase I poisoning by a camptothecin analog
TLDR
The x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan suggests that there are at least two classes of mutations that can produce a drug-resistant enzyme. Expand
DNA topoisomerase-targeting antitumor drugs can be studied in yeast.
  • J. Nitiss, J. Wang
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1988
TLDR
The antitumor drugs camptothecin and an anilinoacridine, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (mAMSA) are shown to inhibit the growth of Saccharomyces cerevisiae mutants selected for their permeability to other inhibitors. Expand
Evaluation of indenoisoquinoline topoisomerase I inhibitors using a hollow fiber assay.
TLDR
Indenoisoquinoline analogs have been screened in the National Cancer Institute's hollow fiber assay (HFA) and demonstrated significant activity at intraperitoneal and subcutaneous fiber placement sites, along with net cancer cell kill in one or more cell lines. Expand
Repair of topoisomerase I-mediated DNA damage.
TLDR
This chapter reviews the developments in several pathways involved in the repair of Top1 cleavage complexes and the role of Chk1 and Chk2 checkpoint kinases in the cellular responses to Top1 inhibitors. Expand
Topoisomerase I-mediated DNA damage.
TLDR
This review summarizes the various factors that enhance or suppress top1 cleavage complexes and discusses the significance of such effects. Expand
Mechanisms of camptothecin resistance by human topoisomerase I mutations.
TLDR
The crystal structures of two camptothecin-resistant forms of human topoisomerase I are presented and a well-ordered water molecule replaces the hydrophobic phenylalanine side-chain in the Phe361Ser structure, advancing the understanding of the mechanism of cell poisoning by camPTothecin. Expand
Inhibition of Human Tyrosyl-DNA Phosphodiesterase by Aminoglycoside Antibiotics and Ribosome Inhibitors
TLDR
It is reported that neomycin inhibits Tdp1 more effectively than the related aminoglycosides paromomycin and lividomycin A and is greatest at low pH. Expand
A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex
TLDR
The interfacial inhibition paradigm described for topoisomerase I inhibitors can be generalized to a variety of natural products that trap macromolecular complexes as they undergo catalytic conformational changes that create hotspots for drug binding. Expand
...
1
2
3
4
5
...