Ribonucleotide Reductase as a Target to Control Cancer Proliferation
Pp. 363-406 (44)
Nuno M.F.S.A. Cerqueira, Narayana S.H.N. Moorthy, Pedro A. Fernandes and Maria J. Ramos
Ribonucleotide Reductase (RNR) plays a critical role in DNA synthesis, and
is a well-recognized target for cancer chemotherapeutic and antiviral agents. RNR
inhibition precludes DNA transcription and repair, from which results cell apoptosis.
Many regulation checkpoints concerning RNR activity have been unravelled through
the last two decades, with potential use to inhibit enzyme activity. This was
accomplished by researchers from different but complementary areas from which
several and different inhibitors have resulted. The volume of these studies has generated
over 5000 articles since the discovery of RNR in 1960. Some of these compounds have
already been approved by FDA and EMEA for the treatment of specific types of cancer,
as it is the case of gemcitabine, fluoromethylene and hydroxyurea. This chapter
summarizes patents and papers during the period 1958-2012 dealing with the present
understanding of ribonucleotidereductase biochemistry, mechanism of action and the
most relevant data concerning RNR inhibition. Special attention is given to the
inhibitors that have been patented and are currently in clinical use.
Allosteric, antisense, cancer, clinical trials, dimerization, DNA, FDA,
gemcitabine, GTI-2040, HIV, hydroxyurea, inhibitors, iron chelators,
mechanisms, nucleotides, radical-scavengers, ribonucleotide reductase, substrate
analogues, tezacitabine, theoretical results.
REQUINTE, Faculty of Sciences, University of Porto, Rua do Campo Alegre s/n 4169-007 Porto – Portugal.