Design, synthesis, and evaluation of small molecule Hsp90 probes
Tony Taldone,Danuta Zatorska,Pallav D. Patel,Hongliang Zong,Anna Rodina,James H. Ahn,Kamalika Moulick,Monica L. Guzman,Gabriela Chiosis +8 more
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TLDR
The synthesis of chemical tools for three Hsp90 inhibitor classes will be useful for probing tumor-by-tumor the HSp90 complexes isolated by specific inhibitors, and will lead to better understanding of tumor specific molecular markers to aid in their clinical development.About:
This article is published in Bioorganic & Medicinal Chemistry.The article was published on 2011-04-15 and is currently open access. It has received 49 citations till now. The article focuses on the topics: Hsp90 inhibitor & Docking (molecular).read more
Citations
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Book ChapterDOI
Hsp90: Structure and Function.
TL;DR: The focus of this review is the structural and mechanistic studies which have been performed in order to understand how this important chaperone acts on a wide variety of different proteins (its client proteins) and cellular processes.
Journal ArticleDOI
The epichaperome is an integrated chaperome network that facilitates tumour survival
Anna Rodina,Tai Wang,Pengrong Yan,Erica DaGama Gomes,Mark Dunphy,Nagavarakishore Pillarsetty,John Koren,John F. Gerecitano,Tony Taldone,Hongliang Zong,Eloisi Caldas-Lopes,Mary L. Alpaugh,Adriana D. Corben,Matthew Riolo,Brad Beattie,Christina Pressl,Radu I Peter,Chao Xu,Robert Trondl,Hardik J. Patel,Fumiko Shimizu,Alexander Bolaender,Chenghua Yang,Palak Panchal,Mohammad F. Farooq,Sarah Kishinevsky,Shanu Modi,Oscar Lin,Feixia Chu,Sujata Patil,Hediye Erdjument-Bromage,Pat Zanzonico,Clifford A. Hudis,Lorenz Studer,Gail J. Roboz,Ethel Cesarman,Leandro Cerchietti,Ross L. Levine,Ari Melnick,Steven M. Larson,Jason S. Lewis,Monica L. Guzman,Gabriela Chiosis,Gabriela Chiosis +43 more
TL;DR: It is found that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically ‘rewired’ to form a network of stable, survival-facilitating, high-molecular-weight complexes.
Journal ArticleDOI
Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2
Pallav D. Patel,Pengrong Yan,Paul M. Seidler,Paul M. Seidler,Hardik J. Patel,Weilin Sun,Chenghua Yang,Nanette L.S. Que,Nanette L.S. Que,Tony Taldone,Paola Finotti,Ralph Stephani,Daniel T. Gewirth,Daniel T. Gewirth,Gabriela Chiosis +14 more
TL;DR: It is shown that Grp94 selectivity is due to the insertion of these compounds into a new allosteric pocket, and new mechanistic evidence explaining why selective Grp 94 inhibition is particularly efficacious in certain breast cancers is provided.
Journal ArticleDOI
Small molecule modulators of protein-protein interactions: selected case studies.
Madhu Aeluri,Srinivas Chamakuri,Bhanudas Dasari,Shiva Krishna Reddy Guduru,Ravikumar Jimmidi,Srinivas Jogula,Prabhat Arya +6 more
TL;DR: Protein−Protein Interactions Centered on the Inhibitors of Apoptosis Proteins (IAPs) and Synthetic Small Molecules and their Derivatives, and the Unexpected Discovery of First Bivalent SMAC Mimetic AF.
Journal ArticleDOI
Synthesis and evaluation of new Hsp90 inhibitors based on a 1,4,5-trisubstituted 1,2,3-triazole scaffold
Maurizio Taddei,Serena Ferrini,Luca Giannotti,Massimo Corsi,Fabrizio Manetti,Giuseppe Giannini,Loredana Vesci,Ferdinando Maria Milazzo,Domenico Alloatti,Mario B. Guglielmi,Massimo Castorina,Maria Luisa Cervoni,Marcella Barbarino,Rosanna Foderà,Valeria Carollo,Claudio Pisano,Silvia Armaroli,Walter Cabri +17 more
TL;DR: In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922, and one of them, (compound 18, SST0287CL1) was selected for further investigation as the most promising drug candidate.
References
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TL;DR: In this article, the parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described, and the parameters for both torsional and non-bonded energy properties have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER force field.
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Thomas A. Halgren,Robert B. Murphy,Richard A. Friesner,Hege S. Beard,Leah L. Frye,W. Thomas Pollard,Jay L. Banks +6 more
TL;DR: Comparisons to results for the thymidine kinase and estrogen receptors published by Rognan and co-workers show that Glide 2.5 performs better than GOLD 1.1, FlexX 1.8, or DOCK 4.01.
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