Ribonucleotide reductase inhibitors and future drug design

J. Shao, B. Zhou, Bernard Chu, Y. Yen

研究成果: 雜誌貢獻回顧型文獻同行評審

239 引文 斯高帕斯(Scopus)

摘要

Ribonucleotide reductase (RR) is a multisubunit enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides, which are building blocks for DNA replication and repair. The key role of RR in DNA synthesis and cell growth control has made it an important target for anticancer therapy. Increased RR activity has been associated with malignant transformation and tumor cell growth. Efforts for new RR inhibitors have been made in basic and translational research. In recent years, several RR inhibitors, including Triapine, Gemcitabine, and GTI-2040, have entered clinical trial or application. Furthermore, the discovery of p53R2, a p53-inducible form of the small subunit of RR, raises the interest to develop subunit-specific RR inhibitors for cancer treatment. This review compiles recent studies on (1) the structure, function, and regulation of two forms of RR; (2) the role in tumorigenesis of RR and the effect of RR inhibition in cancer treatment; (3) the classification, mechanisms of action, antitumor activity, and clinical trial and application of new RR inhibitors that have been used in clinical cancer chemotherapy or are being evaluated in clinical trials; (4) novel approaches for future RR inhibitor discovery.

原文英語
頁(從 - 到)409-431
頁數23
期刊Current Cancer Drug Targets
6
發行號5
DOIs
出版狀態已發佈 - 2006
對外發佈

ASJC Scopus subject areas

  • 藥學科學
  • 癌症研究

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