Methods to validate Hsp90 inhibitor specificity, to identify off-target effects, and to rethink approaches for further clinical development

Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability

(2017) Pascal Leuenberger et al.   SCIENCE

An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans

(2017) Abbey D. Zuehlke et al.   Nature Communications

The Cellular Thermal Shift Assay: A Novel Biophysical Assay for In Situ Drug Target Engagement and Mechanistic Biomarker Studies

(2016) Daniel Martinez Molina et al.   Annual Review of Pharmacology and Toxicology

Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells

(2016) R. Ferraldeschi et al.   CANCER RESEARCH

Paralog Specific Hsp90 Inhibitors - A Brief History and a Bright Future

(2016) Daniel T. Gewirth   CURRENT TOPICS IN MEDICINAL CHEMISTRY

The epichaperome is an integrated chaperome network that facilitates tumour survival

(2016) Anna Rodina et al.   NATURE

Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression

(2016) M Zou et al.   ONCOGENE

Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β

(2016) Kendrick H. Yim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural and functional basis of protein phosphatase 5 substrate specificity

(2016) Jasmeen Oberoi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase

(2016) K. A. Verba et al.   SCIENCE

Dynamical Structures of Hsp70 and Hsp70-Hsp40 Complexes

(2016) Thomas Reid Alderson et al.   STRUCTURE

Diverging Novobiocin Anti-Cancer Activity from Neuroprotective Activity through Modification of the Amide Tail

(2016) Suman Ghosh et al.   ACS Medicinal Chemistry Letters

The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding

(2016) Mark R. Woodford et al.   Nature Communications

Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma Sensitivity and Selectivity to Hsp90 Inhibitors

(2016) Mark R. Woodford et al.   Cell Reports

Molecular mechanism of thermosensory function of human heat shock transcription factor Hsf1

(2016) Nikolai Hentze et al.   eLife

Alternative splicing of the cell fate determinant Numb in hepatocellular carcinoma

(2015) Yinying Lu et al.   HEPATOLOGY

Vibsanin B Preferentially Targets HSP90β, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis

(2015) Bai-Xin Ye et al.   JOURNAL OF IMMUNOLOGY

High-throughput functional genomics using CRISPR–Cas9

(2015) Ophir Shalem et al.   NATURE REVIEWS GENETICS

c-Abl Mediated Tyrosine Phosphorylation of Aha1 Activates Its Co-chaperone Function in Cancer Cells

(2015) Diana M. Dunn et al.   Cell Reports

A Hyperactive Signalosome in Acute Myeloid Leukemia Drives Addiction to a Tumor-Specific Hsp90 Species

(2015) Hongliang Zong et al.   Cell Reports

Targeting Heat-Shock Protein 90 (HSP90) as a Complementary Strategy to Immune Checkpoint Blockade for Cancer Therapy

(2015) D. A. Proia et al.   Cancer Immunology Research

Posttranslational modification and conformational state of Heat Shock Protein 90 differentially affect binding of chemically diverse small molecule inhibitors

(2015) Kristin Beebe et al.   Oncotarget

A Quantitative Chaperone Interaction Network Reveals the Architecture of Cellular Protein Homeostasis Pathways

(2014) Mikko Taipale et al.   CELL

Interplay of Acetyltransferase EP300 and the Proteasome System in Regulating Heat Shock Transcription Factor 1

(2014) Swasti Raychaudhuri et al.   CELL

N-acetylcysteine prevents the geldanamycin cytotoxicity by forming geldanamycin–N-acetylcysteine adduct

(2014) Petr Mlejnek et al.   CHEMICO-BIOLOGICAL INTERACTIONS

Chemical biology approaches to target validation in cancer

(2014) Julian Blagg et al.   CURRENT OPINION IN PHARMACOLOGY

Discovery and Optimization of 4,5-Diarylisoxazoles as Potent Dual Inhibitors of Pyruvate Dehydrogenase Kinase and Heat Shock Protein 90

(2014) Tao Meng et al.   JOURNAL OF MEDICINAL CHEMISTRY

TAS-116, a Highly Selective Inhibitor of Heat Shock Protein 90  and  , Demonstrates Potent Antitumor Activity and Minimal Ocular Toxicity in Preclinical Models

(2014) S. Ohkubo et al.   MOLECULAR CANCER THERAPEUTICS

Asymmetric Hsp90 N Domain SUMOylation Recruits Aha1 and ATP-Competitive Inhibitors

(2014) Mehdi Mollapour et al.   MOLECULAR CELL

HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models

(2014) Luke Whitesell et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Tracking cancer drugs in living cells by thermal profiling of the proteome

(2014) M. M. Savitski et al.   SCIENCE

Development of a High-Throughput Screening Cancer Cell-Based Luciferase Refolding Assay for Identifying Hsp90 Inhibitors

(2013) Takrima Sadikot et al.   ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES

Target deconvolution techniques in modern phenotypic profiling

(2013) Jiyoun Lee et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Learning from Nature: Advances in Geldanamycin- and Radicicol-Based Inhibitors of Hsp90

(2013) Russell R. A. Kitson et al.   JOURNAL OF ORGANIC CHEMISTRY

Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis

(2013) S. Yoshida et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells

(2013) Ophir Shalem et al.   SCIENCE

Hsp90@chromatin.nucleus: an emerging hub of a networker

(2013) Ritwick Sawarkar et al.   TRENDS IN CELL BIOLOGY

Preface to Hsp90

(2012) Didier Picard   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

A highly selective Hsp90 affinity chromatography resin with a cleavable linker

(2012) Philip F. Hughes et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Hsp90 Globally Targets Paused RNA Polymerase to Regulate Gene Expression in Response to Environmental Stimuli

(2012) Ritwick Sawarkar et al.   CELL

HSF1 Drives a Transcriptional Program Distinct from Heat Shock to Support Highly Malignant Human Cancers

(2012) Marc L. Mendillo et al.   CELL

Hsp90 Molecular Chaperone Inhibitors: Are We There Yet?

(2012) L. Neckers et al.   CLINICAL CANCER RESEARCH

EC144 Is a Potent Inhibitor of the Heat Shock Protein 90

(2012) Jiandong Shi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of a Grp94 inhibitor

(2012) Adam S. Duerfeldt et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Heat shock protein 90  (HSP90 ), a substrate and chaperone of DNA-PK necessary for the apoptotic response

(2012) S. Solier et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects

(2012) C. T. Chan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Elucidation of the Hsp90 C-Terminal Inhibitor Binding Site

(2011) Robert L. Matts et al.   ACS Chemical Biology

Using the Heat-Shock Response To Discover Anticancer Compounds that Target Protein Homeostasis

(2011) Sandro Santagata et al.   ACS Chemical Biology

Regulation of HSF1 Function in the Heat Stress Response: Implications in Aging and Disease

(2011) Julius Anckar et al.   Annual Review of Biochemistry

Post-translational modifications of Hsp90 and their contributions to chaperone regulation

(2011) Mehdi Mollapour et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells

(2011) Jeffery D Eskew et al.   BMC CANCER

A yeast-based screen reveals that sulfasalazine inhibits tetrahydrobiopterin biosynthesis

(2011) Christopher Chidley et al.   Nature Chemical Biology

Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90

(2011) Kamalika Moulick et al.   Nature Chemical Biology

Benzoquinone ansamycin 17AAG binds to mitochondrial voltage-dependent anion channel and inhibits cell invasion

(2011) Q. Xie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Protein Homeostasis and the Phenotypic Manifestation of Genetic Diversity: Principles and Mechanisms

(2010) Daniel F. Jarosz et al.   Annual Review of Genetics

Mutations that increase both Hsp90 ATPase activity in vitro and Hsp90 drug resistance in vivo

(2010) Anna Zurawska et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

A systematic protocol for the characterization of Hsp90 modulators

(2010) Robert L. Matts et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Application of Chemoproteomics to Drug Discovery: Identification of a Clinical Candidate Targeting Hsp90

(2010) Patrick Fadden et al.   CHEMISTRY & BIOLOGY

Reactive oxygen species mediate hepatotoxicity induced by the Hsp90 inhibitor geldanamycin and its analogs

(2010) Yuval Samuni et al.   FREE RADICAL BIOLOGY AND MEDICINE

Swe1Wee1-Dependent Tyrosine Phosphorylation of Hsp90 Regulates Distinct Facets of Chaperone Function

(2010) Mehdi Mollapour et al.   MOLECULAR CELL

Modulation of Heat Shock Transcription Factor 1 as a Therapeutic Target for Small Molecule Intervention in Neurodegenerative Disease

(2010) Daniel W. Neef et al.   PLOS BIOLOGY

Structural Basis of the Radicicol Resistance Displayed by a Fungal Hsp90

(2009) Chrisostomos Prodromou et al.   ACS Chemical Biology

Modulation of Hsf1 activity by novobiocin and geldanamycin

(2009) Renaud Conde et al.   Biochemistry and Cell Biology

Assays for Identification of Hsp90 Inhibitors and Biochemical Methods for Discriminating their Mechanism of Action

(2009) Robert Matts et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Inhibiting the transcription factor HSF1 as an anticancer strategy

(2009) Luke Whitesell et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Role of oxidative stress in geldanamycin-induced cytotoxicity and disruption of Hsp90 signaling complex

(2009) Christina B. Clark et al.   FREE RADICAL BIOLOGY AND MEDICINE

Heat-Shock Factor 1 Controls Genome-wide Acetylation in Heat-shocked Cells

(2009) Sabrina Fritah et al.   MOLECULAR BIOLOGY OF THE CELL

Target profiling of small molecules by chemical proteomics

(2009) Uwe Rix et al.   Nature Chemical Biology

Recent advances and method development for drug target identification

(2009) Janet N.Y. Chan et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

(−)-Epigallocatechin-3-gallate Is a Novel Hsp90 Inhibitor†

(2008) Zhengyu Yin et al.   BIOCHEMISTRY

Silencing of HSP90 Cochaperone AHA1 Expression Decreases Client Protein Activation and Increases Cellular Sensitivity to the HSP90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin

(2008) J. L. Holmes et al.   CANCER RESEARCH

NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis

(2008) S. A. Eccles et al.   CANCER RESEARCH

p23/Sba1p Protects against Hsp90 Inhibitors Independently of Its Intrinsic Chaperone Activity

(2008) F. Forafonov et al.   MOLECULAR AND CELLULAR BIOLOGY

4,5-Diarylisoxazole Hsp90 Chaperone Inhibitors: Potential Therapeutic Agents for the Treatment of Cancer

(2007) Paul A. Brough et al.   JOURNAL OF MEDICINAL CHEMISTRY