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 |
- 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
-
Emerging Role of GPR30/GPER1 in Skeletal Metabolism
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Biodistribution and Pharmacokinetics of PEG-10kDa-Cholecystokinin-10 in Rats After Different Routes of Administration
Current Drug Delivery Do Advanced Glycation End Products (AGEs) Contribute to the Comorbidities of Polycystic Ovary Syndrome (PCOS)?
Current Pharmaceutical Design Marine Derived Anticancer Drugs Targeting Microtubule
Recent Patents on Anti-Cancer Drug Discovery Recent Patents on Genes and Gene Sequences Useful for Developing Breast Cancer Detection Systems
Recent Patents on DNA & Gene Sequences Inhibitors of Post-Translational Modifications of G-Proteins as Probes to Study the Pancreatic β Cell Function: Potential Therapeutic Implications
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Advances in the Systemic Treatment of Neuroendocrine Tumors in the Era of Molecular Therapy
Anti-Cancer Agents in Medicinal Chemistry Editorial (Oxidative Stress in the Vascular Wall: A Useful Physiological Process or a Therapeutic Target in Vascular Disease?)
Recent Patents on Cardiovascular Drug Discovery A Transporter Gene (Sodium Iodide Symporter) for Dual Purposes in Gene Therapy: Imaging and Therapy
Current Gene Therapy Tyrosine Kinase Receptor Transactivation Associated to G Protein-Coupled Receptors
Current Drug Targets The Management of Phosphodiesterase-5 (PDE5) Inhibitor Failure
Current Vascular Pharmacology The Role of Microbiota and Probiotics in Stress-Induced Gastrointestinal Damage
Current Molecular Medicine Ascorbic Acid and Gene Expression: Another Example of Regulation of Gene Expression by Small Molecules?
Current Genomics Mechanism-Based Inactivators as Probes of Cytochrome P450 Structure and Function
Current Drug Metabolism Castration Resistant Prostate Cancer: From Emerging Molecular Pathways to Targeted Therapeutic Approaches
Clinical Cancer Drugs Role of Androgens in Womens Sexual Function & Dysfunction: What Have We Learned in Six Decades?
Current Women`s Health Reviews Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair
CNS & Neurological Disorders - Drug Targets Melatonin and Renal Protection: Novel Perspectives from Animal Experiments and Human Studies (Review)
Current Pharmaceutical Design Antimicrobial, In Vitro and In Vivo Antineoplastic Activities, Mechanism of Action, Structural and Thermal Properties of a Small-Novel Pharmaceutical Organometallic Chelate
Mini-Reviews in Medicinal Chemistry Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile
Current Cancer Drug Targets