Abstract
The development of ligands that as single chemical entities are able to modulate multiple epigenetic targets simultaneously (designed epigenetic multiple ligands) is still in its infancy. We are witnessing some advances with combinations of the fused or linked pharmacophores of an epi-drug and other anticancer agents. More recently, however, a very promising approach has been developed in which a single chemical entity exerts several therapeutic activities simultaneously, such as a compound that inhibits several epigenetic enzymes and as a consequence displays multiple biological profiles that address synergistically a particular multifactorial disease. Despite their promiscuity, these multiple epigenetic ligands have exciting conceptual advantages, as they (i) lower the risk of drug-drug interactions compared to cocktails or multicomponent drugs and facilitate ADMET and toxicology studies, (ii) minimize the development of drug resistance, (iii) exploit synergies between the targeted pathways/factors and (iv) can generally be used at lower therapeutically effective concentrations than the single target drugs. The obvious problem with such compounds is to find/design drugs which target multiple effectors with high selectivity and efficiency without displaying extensive off-target effects. In addition, the rational design of multiple epi-ligands is a major challenge. In this review we provide structurally-based principles and the optimization of activities towards the different epigenetic targets.
Keywords: Epigenetics, cancer, chromatin, histones, DNA, enzyme inhibitors, multiple ligands, therapeutic activities, epigenetic multiple ligands, exploit synergies, neurodevelopmentalmalformations, concordant structural, amino acids, embryonal tumors, hydrophobic
Current Topics in Medicinal Chemistry
Title: Epigenetic Multiple Modulators
Volume: 11 Issue: 22
Author(s): Rosana Alvarez, Lucia Altucci, Hinrich Gronemeyer and Angel R. de Lera
Affiliation:
Keywords: Epigenetics, cancer, chromatin, histones, DNA, enzyme inhibitors, multiple ligands, therapeutic activities, epigenetic multiple ligands, exploit synergies, neurodevelopmentalmalformations, concordant structural, amino acids, embryonal tumors, hydrophobic
Abstract: The development of ligands that as single chemical entities are able to modulate multiple epigenetic targets simultaneously (designed epigenetic multiple ligands) is still in its infancy. We are witnessing some advances with combinations of the fused or linked pharmacophores of an epi-drug and other anticancer agents. More recently, however, a very promising approach has been developed in which a single chemical entity exerts several therapeutic activities simultaneously, such as a compound that inhibits several epigenetic enzymes and as a consequence displays multiple biological profiles that address synergistically a particular multifactorial disease. Despite their promiscuity, these multiple epigenetic ligands have exciting conceptual advantages, as they (i) lower the risk of drug-drug interactions compared to cocktails or multicomponent drugs and facilitate ADMET and toxicology studies, (ii) minimize the development of drug resistance, (iii) exploit synergies between the targeted pathways/factors and (iv) can generally be used at lower therapeutically effective concentrations than the single target drugs. The obvious problem with such compounds is to find/design drugs which target multiple effectors with high selectivity and efficiency without displaying extensive off-target effects. In addition, the rational design of multiple epi-ligands is a major challenge. In this review we provide structurally-based principles and the optimization of activities towards the different epigenetic targets.
Export Options
About this article
Cite this article as:
Alvarez Rosana, Altucci Lucia, Gronemeyer Hinrich and R. de Lera Angel, Epigenetic Multiple Modulators, Current Topics in Medicinal Chemistry 2011; 11 (22) . https://dx.doi.org/10.2174/156802611798184436
DOI https://dx.doi.org/10.2174/156802611798184436 |
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
-
Clinical Vignettes: Integrated Care of Cancer Patients by Oncologists and Cardiologists
Current Cardiology Reviews Cardiac Tumors: Clinical Perspective and Therapeutic Considerations
Current Drug Targets Cardiac Side Effects of Chemotherapy: State of Art and Strategies for a Correct Management
Current Vascular Pharmacology Steerable Sheath Technology in the Ablation of Atrial Fibrillation
Recent Patents on Cardiovascular Drug Discovery Acute Myocardial Infarction in Systemic Mastocytosis: Case Report With Literature Review on the Role of Inflammatory Process in Acute Coronary Syndrome
Current Cardiology Reviews Antiangiogenic Therapy and Ovarian Cancer
Current Women`s Health Reviews First Comprehensive Analysis of Outcomes in Adult Patients after Percutaneous Closure of Isolated Secundum Atrial Septal Defects
Cardiovascular & Hematological Agents in Medicinal Chemistry Infective Endocarditis Complicating Hypertrophic Obstructive Cardiomyopathy: Is Antibiotic Prophylaxis Really Unnecessary?
Current Cardiology Reviews Pulmonary Arterial Hypertension in HIV-infected Patients
Current Hypertension Reviews Clinical Applications of Cardiovascular Magnetic Resonance
Current Pharmaceutical Design Kawasakis Disease, Acrodynia, and Mercury
Current Medicinal Chemistry Recurrent Episodes of Pericardial Effusion as Isolated Manifestation of Tuberculosis: Case Report
Current Medical Imaging Indications of Anti-Inflammatory Drugs in Cardiac Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Colchicine: An Ancient Drug with Multiple Benefits
Current Pharmaceutical Design Familial Mediterranean Fever
Current Rheumatology Reviews The Use of Echocardiography in the Critically Ill; The Role of FADE (Fast Assessment Diagnostic Echocardiography) Training
Current Cardiology Reviews Kawasaki Disease and Its Treatment – An Update
Current Rheumatology Reviews Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis
Current Stem Cell Research & Therapy Stroke and COVID-19 Pandemic: The Dilemma
Coronaviruses Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry