Literature DB >> 15974572

Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design.

Brian W Dymock1, Xavier Barril, Paul A Brough, Julie E Cansfield, Andrew Massey, Edward McDonald, Roderick E Hubbard, Allan Surgenor, Stephen D Roughley, Paul Webb, Paul Workman, Lisa Wright, Martin J Drysdale.   

Abstract

The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

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Year:  2005        PMID： 15974572     DOI： 10.1021/jm050355z

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  27 in total

1.  Mechanistic evaluation of the novel HSP90 inhibitor NVP-AUY922 in adult and pediatric glioblastoma.

Authors:  Nathalie Gaspar; Swee Y Sharp; Suzanne A Eccles; Sharon Gowan; Sergey Popov; Chris Jones; Andrew Pearson; Gilles Vassal; Paul Workman
Journal:  Mol Cancer Ther       Date:  2010-05       Impact factor: 6.261

2.  Hot spot analysis for driving the development of hits into leads in fragment-based drug discovery.

Authors:  David R Hall; Chi Ho Ngan; Brandon S Zerbe; Dima Kozakov; Sandor Vajda
Journal:  J Chem Inf Model       Date:  2011-12-15       Impact factor: 4.956

3.  Hit clustering can improve virtual fragment screening: CDK2 and PARP1 case studies.

Authors:  Alexey A Zeifman; Victor S Stroylov; Fedor N Novikov; Oleg V Stroganov; Alexandra L Zakharenko; Svetlana N Khodyreva; Olga I Lavrik; Ghermes G Chilov
Journal:  J Mol Model       Date:  2011-11-09       Impact factor: 1.810

Review 4.  Heat shock proteins as emerging therapeutic targets.

Authors:  Csaba Sõti; Enikõ Nagy; Zoltán Giricz; László Vígh; Péter Csermely; Péter Ferdinandy
Journal:  Br J Pharmacol       Date:  2005-11       Impact factor: 8.739

5.  Benchmarking sets for molecular docking.

Authors:  Niu Huang; Brian K Shoichet; John J Irwin
Journal:  J Med Chem       Date:  2006-11-16       Impact factor: 7.446

6.  Ligand-Binding-Site Structure Refinement Using Molecular Dynamics with Restraints Derived from Predicted Binding Site Templates.

Authors:  Hugo Guterres; Hui Sun Lee; Wonpil Im
Journal:  J Chem Theory Comput       Date:  2019-10-14       Impact factor: 6.006

7.  Divergent synthesis of a pochonin library targeting HSP90 and in vivo efficacy of an identified inhibitor.

Authors:  Sofia Barluenga; Cuihua Wang; Jean-Gonzague Fontaine; Kaïss Aouadi; Kristin Beebe; Shinji Tsutsumi; Len Neckers; Nicolas Winssinger
Journal:  Angew Chem Int Ed Engl       Date:  2008       Impact factor: 15.336

8.  A combined molecular modeling study on a series of pyrazole/isoxazole based human Hsp90α inhibitors.

Authors:  Ying Yang; Huanxiang Liu; Juan Du; Jin Qin; Xiaojun Yao
Journal:  J Mol Model       Date:  2011-03-04       Impact factor: 1.810

Review 9.  The Chemical Biology of Molecular Chaperones--Implications for Modulation of Proteostasis.

Authors:  Kristoffer R Brandvold; Richard I Morimoto
Journal:  J Mol Biol       Date:  2015-05-21       Impact factor: 5.469

10.  Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors targeting the ATP-binding pocket.

Authors:  Shih-Chia Tso; Xiangbing Qi; Wen-Jun Gui; Cheng-Yang Wu; Jacinta L Chuang; Ingrid Wernstedt-Asterholm; Lorraine K Morlock; Kyle R Owens; Philipp E Scherer; Noelle S Williams; Uttam K Tambar; R Max Wynn; David T Chuang
Journal:  J Biol Chem       Date:  2013-12-19       Impact factor: 5.157
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