Abstract
Heat shock proteins (HSP) are a family of highly conserved proteins, whose expression increases in response to stresses that may threaten cell survival. Over the past decade, heat shock protein 90 (Hsp90) has emerged as a potential therapeutic target for cancer as it plays a vital role in normal cell maturation and acts as a molecular chaperone for proper folding, assembly, and stabilization of many oncogenic proteins. To date, a majority of Hsp90 inhibitors that have been discovered are macrocycles. The relatively rigid conformation provided by the macrocyclic scaffold allows for a selective interaction with a biological target such as Hsp90. This review highlights the discovery and development of nine macrocycles that inhibit the function of Hsp90, detailing their potency and the client proteins affected by Hsp90 inhibition.
Keywords: Hsp90, Hsp90 inhibitors, macrocycles, client protein, geldanamycin, 17AAG, 17-DMAG, IPI504, clinical trials, cancer, herbimycin radicicol, pochonin, radanamycin, SanA, di-SanA
Current Topics in Medicinal Chemistry
Title: Macrocyclic Inhibitors of Hsp90
Volume: 10 Issue: 14
Author(s): Victoria A. Johnson, Erinprit K. Singh, Lidia A. Nazarova, Leslie D. Alexander and Shelli R. McAlpine
Affiliation:
Keywords: Hsp90, Hsp90 inhibitors, macrocycles, client protein, geldanamycin, 17AAG, 17-DMAG, IPI504, clinical trials, cancer, herbimycin radicicol, pochonin, radanamycin, SanA, di-SanA
Abstract: Heat shock proteins (HSP) are a family of highly conserved proteins, whose expression increases in response to stresses that may threaten cell survival. Over the past decade, heat shock protein 90 (Hsp90) has emerged as a potential therapeutic target for cancer as it plays a vital role in normal cell maturation and acts as a molecular chaperone for proper folding, assembly, and stabilization of many oncogenic proteins. To date, a majority of Hsp90 inhibitors that have been discovered are macrocycles. The relatively rigid conformation provided by the macrocyclic scaffold allows for a selective interaction with a biological target such as Hsp90. This review highlights the discovery and development of nine macrocycles that inhibit the function of Hsp90, detailing their potency and the client proteins affected by Hsp90 inhibition.
Export Options
About this article
Cite this article as:
A. Johnson Victoria, K. Singh Erinprit, A. Nazarova Lidia, D. Alexander Leslie and R. McAlpine Shelli, Macrocyclic Inhibitors of Hsp90, Current Topics in Medicinal Chemistry 2010; 10 (14) . https://dx.doi.org/10.2174/156802610792232088
DOI https://dx.doi.org/10.2174/156802610792232088 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Carotenoids of Microalgae Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry Is the Epithelial-to-Mesenchymal Transition Clinically Relevant for the Cancer Patient?
Current Pharmaceutical Biotechnology The Life and Death of Protein Kinase C
Current Drug Targets LncRNAs as Architects in Cancer Biomarkers with Interface of Epitranscriptomics- Incipient Targets in Cancer Therapy
Current Cancer Drug Targets The Role of Cytochrome P450 in Cytotoxic Bioactivation: Future Therapeutic Directions
Current Cancer Drug Targets Progress in Imaging Agents of Cell Apoptosis
Anti-Cancer Agents in Medicinal Chemistry Pharmacotherapy in Systemic Lupus Erythematosus
Current Rheumatology Reviews Subject Index To Volume 13
Current Medicinal Chemistry Acute Renal Failure in Different Malignant Tumors
Current Medicinal Chemistry Quantum Dot-Based Nanocomposites for Biomedical Applications
Current Medicinal Chemistry Recent Patents of DNA Methylation Biomarkers in Gastrointestinal Oncology
Recent Patents on DNA & Gene Sequences New Advances of Heparanase in Human Diseases
Mini-Reviews in Medicinal Chemistry Cancer Stem-Cells Patents in the Context of their Therapeutic Purposes: Exploring the Latest Trends (2011-2015)
Recent Patents on Regenerative Medicine MiR-147: Functions and Implications in Inflammation and Diseases
MicroRNA Cancer Proteomics: New Horizons and Insights into Therapeutic Applications
Current Proteomics Botulinum Toxin a in Prostate Disease: A Venom from Bench to Bed-Side
Current Drug Delivery Salidroside - Can it be a Multifunctional Drug?
Current Drug Metabolism Diagnosis and Management of Endocrine Hypertension in Children and Adolescents
Current Pharmaceutical Design Bcl-2 Proteins: Targets and Tools for Chemosensitisation of Tumor Cells
Current Medicinal Chemistry - Anti-Cancer Agents Molecular Targeted Approaches for Treatment of Pancreatic Cancer
Current Pharmaceutical Design