TDP1 represents a promising therapeutic target for overcoming tumor resistance to chemotherapeutic agents: progress and potential.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2024-12-16 DOI:10.1016/j.bioorg.2024.108072
Meimei Zhang, Ziqiang Wang, Yan Su, Wenbo Yan, Yifan Ouyang, Yanru Fan, Yu Huang, Hao Yang
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引用次数: 0

Abstract

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme that plays a crucial role in repairing DNA lesions caused by the entrapment of DNA topoisomerase IB (TOP1)-DNA break-associated crosslinks. TDP1 inhibitors exhibit synergistic effects with TOP1 inhibitors in cancer cells, effectively overcoming resistance to TOP1 inhibitors. Therefore, this approach presents a promising strategy for reversing tumor resistance to TOP1 inhibitors. This review comprehensively outlines the structural and biological features of TDP1, the substrates involved in its catalytic hydrolysis, and its potential as a therapeutic target in oncology. Additionally, we summarize the various screening methods used to identify TDP1 inhibitors, alongside the latest advancements in TDP1 inhibitor research.

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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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