Abstract
Histone deacetylases (HDACs) play a significant role in the proliferation and dissemination of cancer and represent promising epigenetic drug targets. The HDAC inhibitor vorinostat featuring a zinc-binding hydroxamate fragment was already clinically approved. However, HDAC inhibitors containing hydroxamic acids are often hampered by acquired or intrinsic drug resistance and may lead to enhanced tumor aggressiveness. In order to overcome these drawbacks of hydroxamate HDAC inhibitors, a series of multimodal derivatives of this compound class, including such with different zinc-binding groups, was recently developed and showed promising anticancer activity. This review provides an overview of the chemistry and pleiotropic anticancer modes of action of these conceptually new HDAC inhibitors.
Keywords: Anticancer drugs, epigenetics, histone deacetylases, kinases, DNA targeting, HDAC inhibitors, hybrid molecules.
Current Cancer Drug Targets
Title:Multimodal HDAC Inhibitors with Improved Anticancer Activity
Volume: 18 Issue: 1
Author(s): Rainer Schobert and Bernhard Biersack*
Affiliation:
- Organic Chemistry Laboratory, Faculty of Biology, Chemistry and Earth Sciences, University of Bayreuth, Universitatsstrasse 30, 95440 Bayreuth,Germany
Keywords: Anticancer drugs, epigenetics, histone deacetylases, kinases, DNA targeting, HDAC inhibitors, hybrid molecules.
Abstract: Histone deacetylases (HDACs) play a significant role in the proliferation and dissemination of cancer and represent promising epigenetic drug targets. The HDAC inhibitor vorinostat featuring a zinc-binding hydroxamate fragment was already clinically approved. However, HDAC inhibitors containing hydroxamic acids are often hampered by acquired or intrinsic drug resistance and may lead to enhanced tumor aggressiveness. In order to overcome these drawbacks of hydroxamate HDAC inhibitors, a series of multimodal derivatives of this compound class, including such with different zinc-binding groups, was recently developed and showed promising anticancer activity. This review provides an overview of the chemistry and pleiotropic anticancer modes of action of these conceptually new HDAC inhibitors.
Export Options
About this article
Cite this article as:
Schobert Rainer and Biersack Bernhard*, Multimodal HDAC Inhibitors with Improved Anticancer Activity, Current Cancer Drug Targets 2018; 18 (1) . https://dx.doi.org/10.2174/1568009617666170206102613
DOI https://dx.doi.org/10.2174/1568009617666170206102613 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
Related Articles
-
Nanocarriers Assisted siRNA Gene Therapy for the Management of Cardiovascular Disorders
Current Pharmaceutical Design Genomic and Cellular Pathology of Lung Cancer
Current Respiratory Medicine Reviews Functional Roles of the Ca2+-activated K+ Channel, KCa3.1, in Brain Tumors
Current Neuropharmacology A Comprehensive Review on miR-200c, A Promising Cancer Biomarker with Therapeutic Potential
Current Drug Targets Turning Tumor-Promoting Copper into an Anti-Cancer Weapon via High-Throughput Chemistry
Current Medicinal Chemistry Clinical Applications of the Urokinase Receptor (uPAR) for Cancer Patients
Current Pharmaceutical Design Investigations of Malignant Mesothelioma
Current Respiratory Medicine Reviews Direct Evidence on the Immune-Mediated Spontaneous Regression of Human Cancer: An Incentive for Pharmaceutical Companies to Develop a Novel Anti-Cancer Vaccine
Current Pharmaceutical Design Hormetic Potential of Sulforaphane (SFN) in Switching Cells’ Fate Towards Survival or Death
Mini-Reviews in Medicinal Chemistry Dichotomous Life of DNA Binding High Mobility Group Box1 Protein in Human Health and Disease
Current Protein & Peptide Science Studies on Anticancer Activities of Lactoferrin and Lactoferricin
Current Protein & Peptide Science Metabolic Targeting of Cancers: From Molecular Mechanisms to Therapeutic Strategies
Current Medicinal Chemistry Bioconjugation of Ionophore Antibiotics: A Way to Obtain Hybrids with Potent Biological Activity
Mini-Reviews in Organic Chemistry Pharmacophore Modeling and 3D QSAR Studies of Novel Human Carbonic Anhydrase IX Inhibitors
Letters in Drug Design & Discovery Death Receptor Ligands: New Strategies for Combined Treatment with Ionizing Radiation
Current Medicinal Chemistry - Anti-Cancer Agents Epigenetic Regulation of Gene Expression as an Anticancer Drug Target
Current Cancer Drug Targets Adrenomedullin and Nitric Oxide: Implications for the Etiology and Treatment of Primary Brain Tumors
CNS & Neurological Disorders - Drug Targets Plant Ribonucleases and Nucleases as Antiproliferative Agens Targeting Human Tumors Growing in Mice
Recent Patents on DNA & Gene Sequences Selectively Replicating Adenoviruses for Oncolytic Therapy
Current Cancer Drug Targets The Role of Chemotherapy and Radiation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
Current Drug Targets