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Small Molecule Inhibitors of Human DNA Polymerase λ.

Abstract：

:To discover chemical probes to further under-stand the function of individual DNA polymerases, we established a generally applicable high-throughput screening. By applying this technique we discovered three novel inhibitor classes of human DNA polymerase λ (DNA Pol λ), a key enzyme to maintain the genetic integrity of the genome. The rhodanines, classified as an excellent drug scaffold, were found to be the most potent inhibitors for DNA Pol λ. Importantly, they are up to 10 times less active against the highly similar DNA polymerase β. We investigated basic structure activity relationships. Furthermore, the rhodanines showed pharmacological activity in two human cancer cell lines. So the here reported small molecules could serve as useful DNA Pol λ probes and might serve as starting point to develop novel therapeutic agents.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Strittmatter T,Bareth B,Immel TA,Huhn T,Mayer TU,Marx A

doi

10.1021/cb100382m

subject

Has Abstract

pub_date

2011-04-15 00:00:00

pages

314-9

issue

4

eissn

1554-8929

issn

1554-8937

journal_volume

6

pub_type

杂志文章

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