Ribonucleotide reductase inhibitors and future drug design

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

Research output: Contribution to journalReview article

217 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)409-431
Number of pages23
JournalCurrent Cancer Drug Targets
Volume6
Issue number5
DOIs
Publication statusPublished - 2006
Externally publishedYes

Keywords

  • Classification
  • Clinical trial and application
  • Drug discovery
  • Inhibitors
  • Mechanism of action
  • Ribonucleotide reductase
  • Structure and function

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Cancer Research

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