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Current Drug Therapy


ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

New Cancer Chemotherapy Agents: Inhibitors of DNA Polymerase

Author(s): Kengo Sakaguchi and Fumio Sugawara

Volume 3, Issue 1, 2008

Page: [44 - 53] Pages: 10

DOI: 10.2174/157488508783331234

Price: $65


The purpose of this review is 1) to introduce our studies of newly-discovered mammalian DNA polymerase inhibitors; 2) to elucidate their precise molecular action based on three-dimensional structural models and comparisons with the spatial positioning on the smallest DNA polymerase, β, of specific amino acids binding to them; and 3) to document their promising clinical anti-tumor activity. Multiple DNA polymerases have been identified in eukaryotes, and recent investigations have revealed at least sixteen types. An effective approach to study the in vivo roles of each of these is to use selective DNA polymerase inhibitors to distinguish between them. Using a broad natural product screening approach, we have identified many different types of novel DNA polymerase inhibitor which we have exploited to analyze the structure and function of the DNA polymerases. The aim was not only to understand the function of each inhibitor in vitro, but also to develop a drug design strategy for cancer chemotherapy agents. We have found a class of such DNA polymerase inhibitors, the sulfoquinovosylacylglycerols (SQAG), which could represent clinically-promising anti-tumor agents. We discussed about the mechanism of the anti-tumor action, and suggested new concept about cancer chemotherapy.

Keywords: Cancer chemotherapy, DNA polymerase inhibitor, Sulfoquinovosylacylglycerols (SQAG), radiosensitizers, T7 phage display method, computer-simulated molecular design

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