Literature DB >> 28207175

Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads.

Ilda D'Annessa1, Sara Sattin2, Jiahui Tao3, Marzia Pennati4, Carlos Sànchez-Martìn5, Elisabetta Moroni6, Andrea Rasola5, Nadia Zaffaroni4, David A Agard3, Anna Bernardi2, Giorgio Colombo1.   

Abstract

Allosteric compounds that stimulate Hsp90 adenosine triphosphatase (ATPase) activity were rationally designed, showing anticancer potencies in the low micromolar to nanomolar range. In parallel, the mode of action of these compounds was clarified and a quantitative model that links the dynamic ligand-protein cross-talk to observed cellular and in vitro activities was developed. The results support the potential of using dynamics-based approaches to develop original mechanism-based cancer therapeutics.
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entities:  

Keywords:  allostery; drug design; hsp90; modulators; molecular dynamics

Mesh：

Substances：

Year:  2017        PMID： 28207175      PMCID： PMC5927549          DOI： 10.1002/chem.201700169

Source DB:  PubMed          Journal:  Chemistry        ISSN： 0947-6539            Impact factor:   5.236


  22 in total

1.  Exploiting conformational dynamics in drug discovery: design of C-terminal inhibitors of Hsp90 with improved activities.

Authors:  Elisabetta Moroni; Huiping Zhao; Brian S J Blagg; Giorgio Colombo
Journal:  J Chem Inf Model       Date:  2014-01-15       Impact factor: 4.956

2.  Stressing the development of small molecules targeting HSP90.

Authors:  Len Neckers; Jane B Trepel
Journal:  Clin Cancer Res       Date:  2013-10-28       Impact factor: 12.531

Review 3.  HSP90 and the chaperoning of cancer.

Authors:  Luke Whitesell; Susan L Lindquist
Journal:  Nat Rev Cancer       Date:  2005-10       Impact factor: 60.716

Review 4.  Targeting the dynamic HSP90 complex in cancer.

Authors:  Jane Trepel; Mehdi Mollapour; Giuseppe Giaccone; Len Neckers
Journal:  Nat Rev Cancer       Date:  2010-08       Impact factor: 60.716

5.  Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation.

Authors:  Jason E Gestwicki; Gerald R Crabtree; Isabella A Graef
Journal:  Science       Date:  2004-10-29       Impact factor: 47.728

Review 6.  Conformational dynamics of the molecular chaperone Hsp90.

Authors:  Kristin A Krukenberg; Timothy O Street; Laura A Lavery; David A Agard
Journal:  Q Rev Biophys       Date:  2011-03-18       Impact factor: 5.318

7.  Allosteric Regulation Points Control the Conformational Dynamics of the Molecular Chaperone Hsp90.

Authors:  Alexandra Rehn; Elisabetta Moroni; Bettina K Zierer; Franziska Tippel; Giulia Morra; Christine John; Klaus Richter; Giorgio Colombo; Johannes Buchner
Journal:  J Mol Biol       Date:  2016-09-20       Impact factor: 5.469

8.  Synthesis and initial evaluation of YM-08, a blood-brain barrier permeable derivative of the heat shock protein 70 (Hsp70) inhibitor MKT-077, which reduces tau levels.

Authors:  Yoshinari Miyata; Xiaokai Li; Hsiu-Fang Lee; Umesh K Jinwal; Sharan R Srinivasan; Sandlin P Seguin; Zapporah T Young; Jeffrey L Brodsky; Chad A Dickey; Duxin Sun; Jason E Gestwicki
Journal:  ACS Chem Neurosci       Date:  2013-03-20       Impact factor: 4.418

9.  Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors.

Authors:  Katherine M Byrd; Chitra Subramanian; Jacqueline Sanchez; Hashim F Motiwala; Weiya Liu; Mark S Cohen; Jeffrey Holzbeierlein; Brian S J Blagg
Journal:  Chemistry       Date:  2016-04-01       Impact factor: 5.236

10.  Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands.

Authors:  Gerolamo Vettoretti; Elisabetta Moroni; Sara Sattin; Jiahui Tao; David A Agard; Anna Bernardi; Giorgio Colombo
Journal:  Sci Rep       Date:  2016-04-01       Impact factor: 4.379
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  11 in total

1.  Molecular insights into the interaction of Hsp90 with allosteric inhibitors targeting the C-terminal domain.

Authors:  Vasantha Kumar Mv; Radwan Ebna Noor; Rachel E Davis; Zheng Zhang; Edvinas Sipavicius; Dimitra Keramisanou; Brian S J Blagg; Ioannis Gelis
Journal:  Medchemcomm       Date:  2018-07-02       Impact factor: 3.597

Review 2.  New perspectives in cancer drug development: computational advances with an eye to design.

Authors:  Matteo Castelli; Stefano A Serapian; Filippo Marchetti; Alice Triveri; Valentina Pirota; Luca Torielli; Simona Collina; Filippo Doria; Mauro Freccero; Giorgio Colombo
Journal:  RSC Med Chem       Date:  2021-07-07

3.  Machine Learning Prediction of Allosteric Drug Activity from Molecular Dynamics.

Authors:  Filippo Marchetti; Elisabetta Moroni; Alessandro Pandini; Giorgio Colombo
Journal:  J Phys Chem Lett       Date:  2021-04-12       Impact factor: 6.475

4.  Discovery of new molecular entities able to strongly interfere with Hsp90 C-terminal domain.

Authors:  Stefania Terracciano; Alessandra Russo; Maria G Chini; Maria C Vaccaro; Marianna Potenza; Antonio Vassallo; Raffaele Riccio; Giuseppe Bifulco; Ines Bruno
Journal:  Sci Rep       Date:  2018-01-26       Impact factor: 4.379

5.  Allosteric Regulation of Hsp90α's Activity by Small Molecules Targeting the Middle Domain of the Chaperone.

Authors:  Chen Zhou; Chi Zhang; Hongwen Zhu; Zhijun Liu; Haixia Su; Xianglei Zhang; Tingting Chen; Yan Zhong; Huifang Hu; Muya Xiong; Hu Zhou; Yechun Xu; Ao Zhang; Naixia Zhang
Journal:  iScience       Date:  2020-01-21

6.  Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells.

Authors:  Isabelle R Taylor; Victoria A Assimon; Szu Yu Kuo; Silvia Rinaldi; Xiaokai Li; Zapporah T Young; Giulia Morra; Keith Green; Daniel Nguyen; Hao Shao; Sylvie Garneau-Tsodikova; Giorgio Colombo; Jason E Gestwicki
Journal:  Chem Sci       Date:  2020-01-10       Impact factor: 9.825

7.  Dual targeting of HSP70 does not induce the heat shock response and synergistically reduces cell viability in muscle invasive bladder cancer.

Authors:  Thomas Prince; Andrew Ackerman; Alice Cavanaugh; Brielle Schreiter; Brendon Juengst; Chaylen Andolino; John Danella; Mitch Chernin; Heinric Williams
Journal:  Oncotarget       Date:  2018-08-24

Review 8.  Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer.

Authors:  Rosario Avolio; Danilo Swann Matassa; Daniela Criscuolo; Matteo Landriscina; Franca Esposito
Journal:  Biomolecules       Date:  2020-01-14

9.  Design of Disruptors of the Hsp90-Cdc37 Interface.

Authors:  Ilda D'Annessa; Naama Hurwitz; Valentina Pirota; Giovanni Luca Beretta; Stella Tinelli; Mark Woodford; Mauro Freccero; Mehdi Mollapour; Nadia Zaffaroni; Haim Wolfson; Giorgio Colombo
Journal:  Molecules       Date:  2020-01-15       Impact factor: 4.411

Review 10.  Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning.

Authors:  Gennady M Verkhivker; Steve Agajanian; Guang Hu; Peng Tao
Journal:  Front Mol Biosci       Date:  2020-07-09
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