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Issue 3, 2015
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Naturally occurring FANCF–Hes1 complex inhibitors from Wrightia religiosa

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Abstract

The isolation and evaluation of inhibitors of Fanconi F protein (FANCF) – hairy and enhancer of split 1 (Hes1) complex are described. A high-throughput screening assay for small-moleculeinhibitors of the FANCF–Hes1 complex was realized. Successful complex formation between fluorophore (Cy3)-labeled human FANCF and immobilized rat or human HES1 on a microplate was established. Screening of our plant extract library using this system resulted in the isolation of eight natural products, including two new flavonoid glycosides (3 and 4), from Wrightia religiosa. Of these compounds, 3, 5, and 7 showed potent inhibition of the FANCF–Hes1 complex formation. Compound 7 disrupted the FANCF–Hes1 complex more efficiently than the Hes1 dimer.

Graphical abstract: Naturally occurring FANCF–Hes1 complex inhibitors from Wrightia religiosa

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Supplementary files

Article information


Submitted
31 Oct 2014
Accepted
21 Nov 2014
First published
11 Dec 2014

Med. Chem. Commun., 2015,6, 455-460
Article type
Concise Article

Naturally occurring FANCF–Hes1 complex inhibitors from Wrightia religiosa

M. A. Arai, K. Uemura, N. Hamahiga, N. Ishikawa, T. Koyano, T. Kowithayakorn, T. Kaddar, M. Carreau and M. Ishibashi, Med. Chem. Commun., 2015, 6, 455
DOI: 10.1039/C4MD00495G

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