Abstract
This manuscript reviews published Hsp90 inhibitors and Hsp90-binding compounds. The main goal of the article is to overview the structures of existing Hsp90 inhibitors and to draw correlations between compound structure and binding affinity. Furthermore, it is important to emphasize all thermodynamic binding data especially the data that includes the enthalpies, entropies, heat capacities, and the volumes of binding. This information is important for the goal of drawing the principles of a more rational drug design. The distinction between the observed and the intrinsic binding parameters should also be emphasized. Out of nearly 280 compounds surveyed, most could be classified to three chemical groups (resorcinol-bearing, geldanamycin derivatives, and purine-pyrimidine derivatives) and only few of them have determined intrinsic thermodynamic parameters other than the dissociation/inhibition constant. Since most compounds are being developed as anticancer agents, the available cell growth inhibition data is also included. Possible limitations of the use of enzymatic inhibition and the cancer cell growth inhibition data is discussed.
Keywords: Hsp90, isothermal titration calorimetry, ThermoFluor®, thermal shift assay.
Current Protein & Peptide Science
Title:Inhibitor Binding to Hsp90: A Review of Thermodynamic, Kinetic, Enzymatic, and Cellular Assays
Volume: 15 Issue: 3
Author(s): Vilma Petrikaite and Daumantas Matulis
Affiliation:
Keywords: Hsp90, isothermal titration calorimetry, ThermoFluor®, thermal shift assay.
Abstract: This manuscript reviews published Hsp90 inhibitors and Hsp90-binding compounds. The main goal of the article is to overview the structures of existing Hsp90 inhibitors and to draw correlations between compound structure and binding affinity. Furthermore, it is important to emphasize all thermodynamic binding data especially the data that includes the enthalpies, entropies, heat capacities, and the volumes of binding. This information is important for the goal of drawing the principles of a more rational drug design. The distinction between the observed and the intrinsic binding parameters should also be emphasized. Out of nearly 280 compounds surveyed, most could be classified to three chemical groups (resorcinol-bearing, geldanamycin derivatives, and purine-pyrimidine derivatives) and only few of them have determined intrinsic thermodynamic parameters other than the dissociation/inhibition constant. Since most compounds are being developed as anticancer agents, the available cell growth inhibition data is also included. Possible limitations of the use of enzymatic inhibition and the cancer cell growth inhibition data is discussed.
Export Options
About this article
Cite this article as:
Petrikaite Vilma and Matulis Daumantas, Inhibitor Binding to Hsp90: A Review of Thermodynamic, Kinetic, Enzymatic, and Cellular Assays, Current Protein & Peptide Science 2014; 15 (3) . https://dx.doi.org/10.2174/1389203715666140331115032
DOI https://dx.doi.org/10.2174/1389203715666140331115032 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Interleukin-6: A Critical Cytokine in Cancer Multidrug Resistance
Current Pharmaceutical Design The Histone Deacetylase Inhibitor, MS-275 (Entinostat), Downregulates c-FLIP, Sensitizes Osteosarcoma Cells to FasL, and Induces the Regression of Osteosarcoma Lung Metastases
Current Cancer Drug Targets Copper(II) Complexes with Saccharinate and Glutamine as Antitumor Agents: Cytoand Genotoxicity in Human Osteosarcoma Cells
Anti-Cancer Agents in Medicinal Chemistry Phosphonate Emerging Zinc Binding Group in Matrix Metalloproteinase Inhibitors
Current Drug Targets Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin
Current Cancer Drug Targets Electron Spin Resonance as a Powerful Tool for Studying Antioxidants and Radicals
Current Medicinal Chemistry Nanoparticles based on oleate alginate ester as curcumin delivery system
Current Drug Delivery Recent Progress in Therapeutic and Diagnostic Applications of Lanthanides
Mini-Reviews in Medicinal Chemistry ICE Regimen for Relapsed/Refractory Bone and Soft Tissue Sarcomas in Children
Reviews on Recent Clinical Trials A Review of the Recent Developments in Synthetic Anti-Breast Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Natural Polymers Based Hydrogels for Cell Culture Applications
Current Medicinal Chemistry Statins-Mediated Inhibition of Rho GTPases as a Potential Tool in Anti-Tumor Therapy
Mini-Reviews in Medicinal Chemistry Approaches for Administering Chemotherapy in the Intensive Care Unit
Current Drug Safety Inhibition of Cdc42-Interacting Protein 4 (CIP4) Impairs Osteosarcoma Tumor Progression
Current Cancer Drug Targets Emerging Features in the Regulation of MMP-9 Gene Expression for the Development of Novel Molecular Targets and Therapeutic Strategies
Current Drug Targets - Inflammation & Allergy Rheumatoid Nodules and Lung
Current Respiratory Medicine Reviews Osteoimmunology and Beyond
Current Medicinal Chemistry Antioxidant, Antimicrobial and the Phenolic Content of Infusion, Decoction and Methanolic Extracts of Thyme and Rosmarinus Species
Current Pharmaceutical Biotechnology Inhibition of TGF- Signaling for the Treatment of Tumor Metastasis and Fibrotic Diseases
Current Signal Transduction Therapy Probing Gallic Acid for Its Broad Spectrum Applications
Mini-Reviews in Medicinal Chemistry