Abstract
The vitamin D receptor (VDR) is an endocrine member of the nuclear receptor superfamily and binds the biologically most active vitamin D metabolite, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). The VDR ligandbinding domain is a molecular switch, since its ligand-triggered interactions with corepressor and coactivator proteins are the central molecular events of nuclear 1α,25(OH)2D3 signaling. 1α,25(OH)2D3 analogues have been developed with the goal to improve the biological profile of the natural hormone for a therapeutic application either in hyperproliferative diseases, such as psoriasis and different types of cancer, or in bone disorders, such as osteoporosis. Most of the analogues described to date are agonists, with a few having been identified as antagonists. Only the two side chain analogue Gemini and some of its derivatives act under restricted conditions as inverse agonists. In this review we discuss the molecular mechanisms of these different type of analogues based on crystal structure data, molecular dynamics simulations and biochemical assays.
Keywords: Nuclear receptor signaling, vitamin D, vitamin D analogues, vitamin D receptor, coactivator proteins, corepressor proteins
Current Topics in Medicinal Chemistry
Title: Detailed Molecular Understanding of Agonistic and Antagonistic Vitamin D Receptor Ligands
Volume: 6 Issue: 12
Author(s): Carsten Carlberg and Ferdinand Molnar
Affiliation:
Keywords: Nuclear receptor signaling, vitamin D, vitamin D analogues, vitamin D receptor, coactivator proteins, corepressor proteins
Abstract: The vitamin D receptor (VDR) is an endocrine member of the nuclear receptor superfamily and binds the biologically most active vitamin D metabolite, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). The VDR ligandbinding domain is a molecular switch, since its ligand-triggered interactions with corepressor and coactivator proteins are the central molecular events of nuclear 1α,25(OH)2D3 signaling. 1α,25(OH)2D3 analogues have been developed with the goal to improve the biological profile of the natural hormone for a therapeutic application either in hyperproliferative diseases, such as psoriasis and different types of cancer, or in bone disorders, such as osteoporosis. Most of the analogues described to date are agonists, with a few having been identified as antagonists. Only the two side chain analogue Gemini and some of its derivatives act under restricted conditions as inverse agonists. In this review we discuss the molecular mechanisms of these different type of analogues based on crystal structure data, molecular dynamics simulations and biochemical assays.
Export Options
About this article
Cite this article as:
Carlberg Carsten and Molnar Ferdinand, Detailed Molecular Understanding of Agonistic and Antagonistic Vitamin D Receptor Ligands, Current Topics in Medicinal Chemistry 2006; 6 (12) . https://dx.doi.org/10.2174/156802606777864908
DOI https://dx.doi.org/10.2174/156802606777864908 |
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
-
Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair
CNS & Neurological Disorders - Drug Targets Nampt/Visfatin/PBEF: A Functionally Multi-faceted Protein with a Pivotal Role in Malignant Tumors
Current Pharmaceutical Design Telomere Maintenance as Therapeutic Target in Embryonal Tumours
Anti-Cancer Agents in Medicinal Chemistry Testosterone as Potential Effective Therapy in Treatment of Obesity in Men with Testosterone Deficiency: A Review
Current Diabetes Reviews Peroxisome Proliferator-Activated Receptor γ Agonists as Insulin Sensitizers: From the Discovery to Recent Progress
Current Topics in Medicinal Chemistry Clinical Application of Ghrelin
Current Pharmaceutical Design Cognitive Impairment and Diabetes
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Lessons from the Drug Discovery of Lapatinib, a Dual ErbB1/2 Tyrosine Kinase Inhibitor
Current Topics in Medicinal Chemistry Abatacept and Glomerular Diseases: The Open Road for the Second Signal as a New Target is Settled Down
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Benzodiazepines, Amphetamines, Testosterone, and Sildenafil as New Candidate Drugs for Sexual Interest, Desire and/or Arousal Disorder
Current Psychopharmacology Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature
Current Cardiology Reviews The miRNAs and Epithelial-Mesenchymal Transition in Cancers
Current Pharmaceutical Design The Immunomodulatory Effects of Physical Activity
Current Pharmaceutical Design Helicobacter Pylori Infection, Immune Response and Vaccination
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Limitations of Inhibitory Activities of Polyphenols on Furin-Mediated Substrate Processing
Current Medicinal Chemistry Non-transfusion Dependent Thalassemias: A Developing Country Perspective
Current Pediatric Reviews Predicting the Intention to Preconception Care on the Basis of Planning Behavior Theory in Women Referred to the Marriage Counseling Centers in Asadabad in 2015
Current Women`s Health Reviews Failure of Immune Homeostasis - The Consequences of Under and Over Reactivity
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Cellular and Physiological Effects of Arginine
Mini-Reviews in Medicinal Chemistry Sex Steroids in Autoimmune Diseases
Current Topics in Medicinal Chemistry