Novel organic proteasome inhibitors identified by virtual and in vitro screening

Journal of Medicinal Chemistry
Nicolas BasseMichèle Reboud-Ravaux

Abstract

Proteasome inhibition is a promising strategy for treating cancers. Herein, we report the discovery of novel drug-like inhibitors of mammalian proteasome 20S using a multistep structure-based virtual ligand screening strategy. Sulfone- or piperazine-containing hits essentially belong to the under-represented class of noncovalent and nonpeptidic proteasome inhibitors. Several of our compounds act in the micromolar range and are cytotoxic on human tumoral cell lines. Optimization of these molecules could lead to better anticancer therapy.

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Citations

Jun 16, 2012·Journal of the American Chemical Society·Donghui WeiChang-Guo Zhan
Apr 4, 2013·Journal of Medicinal Chemistry·Sevil OzcanSaïd M Sebti
Jun 29, 2011·Future Medicinal Chemistry·Chenzhong LiaoMarc C Nicklaus
Dec 11, 2013·European Journal of Medicinal Chemistry·Makoto HasegawaTamio Mizukami
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Mar 1, 2011·Expert Opinion on Drug Discovery·David LagorceMaria A Miteva
Dec 1, 2010·Expert Opinion on Drug Discovery·Lyuben TsvetkovKenyon G Daniel
Jun 1, 2014·Expert Opinion on Drug Discovery·Chiara PautassoAntonio Palumbo
Mar 24, 2012·European Journal of Medicinal Chemistry·Xavier MaréchalJoëlle Vidal
Jul 10, 2010·Biochimie·Geoffroy de Bettignies, Olivier Coux
Feb 7, 2015·Journal of Medicinal Chemistry·Zachary MillerKyung Bo Kim
Feb 22, 2017·Molecular Informatics·Maria A Miteva, Bruno O Villoutreix
May 29, 2015·Organic & Biomolecular Chemistry·Donghui WeiChang-Guo Zhan
Mar 4, 2014·Medicinal Research Reviews·Nicola MicaleMaria Zappalà
Jul 22, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Romina A GuedesRita C Guedes
Apr 27, 2016·Bioorganic & Medicinal Chemistry·Tanner J McDanielJetze J Tepe
Jun 26, 2010·Journal of Medicinal Chemistry·Luke R OdellAdam McCluskey
Oct 22, 2014·Journal of Medicinal Chemistry·Audrey DesvergneJoëlle Vidal

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