Ribonucleotide reductase: a critical enzyme for cancer chemotherapy and antiviral agents.
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, and from which several and different inhibitors have resulted. The volume of these studies has generated over 4000 articles since the discovery of RNR in 1960. This review summarises patents and papers during the period 1958 - 2005 dealing with the present understanding of ribonucleotide reductase 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.
Cerqueira
Nuno M F S A
NM
REQUIMTE / Faculdade de Ciências do Porto, Rua Campo Alegre, 687, 4169-007 Porto, Portugal. nscerque@fc.up.pt
Fernandes
Pedro A
PA
Ramos
Maria J
MJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D011487:Protein Conformation; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D012264:Ribonucleotide Reductases