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Mizushina, Y. et al.

Yoshiyuki Mizushina, Naoki Maeda, Isoko Kuriyama, Hiromi Yoshida,

Dehydroaltenusin is a specific inhibitor of mammalian DNA polymerase α.

Introduction: We carried out a screen for small molecule selective inhibitors of eukaryotic DNA polymerases (pols). Dehydroaltenusin, isolated from a fungus (Alternaria tenuis), was found to be a specific inhibitor of pol α. Areas covered: We succeeded in chemically synthesizing dehydroaltenusin along with five analogs. Of these compounds, dehydroaltenusin was the strongest and most specific inhibitor of mammalian pol α, with an IC(50) value of 0.68 μM. The inhibitory mode of action of dehydroaltenusin against mammalian pol α activity was competitive with respect to the DNA template primer and non-competitive with respect to the 2'-deoxyribonucleoside 5'-triphosphate substrate. Dehydroaltenusin inhibited the cell proliferation of a human cervical cancer cell line, HeLa, by arresting the cells at the S-phase, and preventing the incorporation of thymidine into the cells. These observations indicate that dehydroaltenusin blocks in vivo DNA replication by inhibiting pol α. Expert opinion: Dehydroaltenusin was effective in suppressing the growth of solid tumors and, therefore, is of interest as a candidate drug for anti-cancer treatment.[1]

References

Dehydroaltenusin is a specific inhibitor of mammalian DNA polymerase α. Mizushina, Y., Maeda, N., Kuriyama, I., Yoshida, H. Expert. Opin. Investig. Drugs (2011) [Pubmed]

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