Abstract
Heat shock proteins (HSPs) present as a double edged sword. While they play an important role in maintaining protein homeostasis in a normal cell, cancer cells have evolved to co-opt HSP function to promote their own survival. As a result, HSPs such as HSP90 have attracted a great deal of interest as a potential anticancer target. These efforts have resulted in over 20 distinct compounds entering clinical evaluation for the treatment of cancer. However, despite the potent anticancer activity demonstrated in preclinical models, to date no HSP90 inhibitor has obtained regulatory approval. In this review we discuss the unique challenges faced in targeting HSPs that have likely contributed to their lack of progress in the clinic and suggest ways to overcome these so that the enormous potential of these compounds to benefit patients can finally be realized. We also provide a guideline for the future development of HSP-targeted agents based on the many lessons learned during the last two decades in developing HSP90 inhibitors.
Keywords: HSP90, Chaperone, Inhibitor, Cancer, N-Terminal.
Current Topics in Medicinal Chemistry
Title:Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease
Volume: 16 Issue: 25
Author(s): Liza Shrestha, Alexander Bolaender, Hardik J. Patel and Tony Taldone
Affiliation:
Keywords: HSP90, Chaperone, Inhibitor, Cancer, N-Terminal.
Abstract: Heat shock proteins (HSPs) present as a double edged sword. While they play an important role in maintaining protein homeostasis in a normal cell, cancer cells have evolved to co-opt HSP function to promote their own survival. As a result, HSPs such as HSP90 have attracted a great deal of interest as a potential anticancer target. These efforts have resulted in over 20 distinct compounds entering clinical evaluation for the treatment of cancer. However, despite the potent anticancer activity demonstrated in preclinical models, to date no HSP90 inhibitor has obtained regulatory approval. In this review we discuss the unique challenges faced in targeting HSPs that have likely contributed to their lack of progress in the clinic and suggest ways to overcome these so that the enormous potential of these compounds to benefit patients can finally be realized. We also provide a guideline for the future development of HSP-targeted agents based on the many lessons learned during the last two decades in developing HSP90 inhibitors.
Export Options
About this article
Cite this article as:
Shrestha Liza, Bolaender Alexander, Patel J. Hardik and Taldone Tony, Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease, Current Topics in Medicinal Chemistry 2016; 16 (25) . https://dx.doi.org/10.2174/1568026616666160413141911
DOI https://dx.doi.org/10.2174/1568026616666160413141911 |
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
-
Targeting Established Tumor Vasculature: A Novel Approach to Cancer Treatment
Current Cancer Therapy Reviews ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development
Current Pharmaceutical Design DNA Double Strand Break Repair - Related Synthetic Lethality
Current Medicinal Chemistry Targeting Heme for the Identification of Cytotoxic Agents
Anti-Cancer Agents in Medicinal Chemistry Repositioning of DHFR Inhibitors
Current Topics in Medicinal Chemistry Therapeutic Outcomes in AIDS-Associated Kaposi's Sarcoma Patients on Antiretroviral Therapy Treated with Chemotherapy at Two Tertiary Hospitals in Lusaka, Zambia
Current HIV Research The Re-Emergence of Aerosol Gene Delivery: A Viable Approach to Lung Cancer Therapy
Current Cancer Drug Targets Substrate Spectra of Nucleoside Phosphorylases and their Potential in the Production of Pharmaceutically Active Compounds
Current Pharmaceutical Design Organophosphorus Chemistry: Therapeutic Intervention in Mechanisms of Viral and Cellular Replication
Current Organic Chemistry Endothelin-1 and Angiogenesis in Cancer
Current Vascular Pharmacology Adrenomedullin and Nitric Oxide: Implications for the Etiology and Treatment of Primary Brain Tumors
CNS & Neurological Disorders - Drug Targets Virtual Screening and Toxicology Prediction of Novel Potential Non- Nucleoside Reverse Transcriptase Inhibitors
Current Bioactive Compounds Drug Targeting to the Brain - A Review
Current Nanoscience Potential Role of <i>In Vitro-In Vivo</i> Correlations (IVIVC) for the Development of Plant-Derived Anticancer Drugs
Current Drug Targets Genomic and Cellular Pathology of Lung Cancer
Current Respiratory Medicine Reviews New Targets for the Modulation of Radiation Response - Selective Inhibition of the Enzyme Cyclooxygenase 2
Current Medicinal Chemistry - Anti-Cancer Agents Heterocyclic Chalcone Analogues as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Electrotransfer as a Non Viral Method of Gene Delivery
Current Gene Therapy SRC: Regulation, Role in Human Carcinogenesis and Pharmacological Inhibitors
Current Pharmaceutical Design Cardiotonic Steroids, Hypertension and Cardiovascular Disease
Current Hypertension Reviews