Abstract
The calcium sensing receptor (CaR) is a G protein-coupled receptor (GPCR) that plays a fundamental role in serum calcium homeostasis. The CaR is expressed on the chief cells of the parathyroid gland and is responsible for controlling the secretion of parathyroid hormone (PTH). PTH acts on several organs including the bone, kidney, and intestine to tightly regulate the concentration of serum calcium. Substances other than calcium that activate the CaR are referred to as calcimimetics. Calcimimetics that bind to the CaR as agonists are referred to as type I. Type II calcimimetics bind to a site that is distinct from the physiological ligand and function as positive allosteric modulators of the CaR. Type II calcimimetics amplify the sensitivity of the CaR to serum calcium and are thus able to lower the concentration of serum PTH. Calcimimetics are being pursued as therapeutics for the treatment of disorders that are characterized by elevated levels of PTH such as primary and secondary hyperparathyroidism (primary HPT and secondary HPT). In this review, we provide an overview of key results in the discovery of cinacalcet HCl (Sensipar® in the US, Mimpara® in Europe). In addition, other recently disclosed type II calcimimetics are discussed.
Keywords: Calcium sensing receptor, calcimimetics, cinacalcet, hyperparathyroidism, Mimpara®, parathyroid hormone, R-568, Sensipar®
Current Medicinal Chemistry
Title: Calcium Sensing Receptor Activators: Calcimimetics
Volume: 14 Issue: 28
Author(s): Paul E. Harrington and Christopher Fotsch
Affiliation:
Keywords: Calcium sensing receptor, calcimimetics, cinacalcet, hyperparathyroidism, Mimpara®, parathyroid hormone, R-568, Sensipar®
Abstract: The calcium sensing receptor (CaR) is a G protein-coupled receptor (GPCR) that plays a fundamental role in serum calcium homeostasis. The CaR is expressed on the chief cells of the parathyroid gland and is responsible for controlling the secretion of parathyroid hormone (PTH). PTH acts on several organs including the bone, kidney, and intestine to tightly regulate the concentration of serum calcium. Substances other than calcium that activate the CaR are referred to as calcimimetics. Calcimimetics that bind to the CaR as agonists are referred to as type I. Type II calcimimetics bind to a site that is distinct from the physiological ligand and function as positive allosteric modulators of the CaR. Type II calcimimetics amplify the sensitivity of the CaR to serum calcium and are thus able to lower the concentration of serum PTH. Calcimimetics are being pursued as therapeutics for the treatment of disorders that are characterized by elevated levels of PTH such as primary and secondary hyperparathyroidism (primary HPT and secondary HPT). In this review, we provide an overview of key results in the discovery of cinacalcet HCl (Sensipar® in the US, Mimpara® in Europe). In addition, other recently disclosed type II calcimimetics are discussed.
Export Options
About this article
Cite this article as:
Harrington E. Paul and Fotsch Christopher, Calcium Sensing Receptor Activators: Calcimimetics, Current Medicinal Chemistry 2007; 14 (28) . https://dx.doi.org/10.2174/092986707782794096
DOI https://dx.doi.org/10.2174/092986707782794096 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Cytotoxic Potential of Phenothiazines
Current Drug Targets Recombinant Human Semenogelin-1 (Sg1) and Sg1 (1-159) form Detergent Stable Amyloid like Aggregates in vitro
Protein & Peptide Letters Epidemiology, Clinical Presentation and Treatment of Uveal Melanoma
Clinical Cancer Drugs Current and Potential Anticancer Drugs Targeting Members of the UHRF1 Complex Including Epigenetic Modifiers
Recent Patents on Anti-Cancer Drug Discovery The Chemical Methods of Disulfide Bond Formation and Their Applications to Drug Conjugates
Current Organic Chemistry Neonatal Germ Cell Tumors
Current Pediatric Reviews Autologous Formalin-Fixed Tumor Vaccine
Current Pharmaceutical Design Development of FXR, PXR and CAR Agonists and Antagonists for Treatment of Liver Disorders
Current Topics in Medicinal Chemistry The Protein-Protein Interaction-Mediated Inactivation of PTEN
Current Molecular Medicine TRIM65 in White Matter Lesions, Innate Immunity, and Tumor
Current Molecular Pharmacology A Survey on Synthesis Processes of Structured Materials for Biomedical Applications: Iron-based Magnetic Nanoparticles, Polymeric Materials and Polymerization Processes
Current Pharmaceutical Design ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms
Current Analytical Chemistry Immunotherapy of Pancreatic Carcinoma
Reviews on Recent Clinical Trials Therapeutic Effects of Quetiapine on Memory Deficit and Brain β-Amyloid Plaque Pathology in a Transgenic Mouse Model of Alzheimer’s Disease
Current Alzheimer Research Nanomedicine to Overcome Cancer Multidrug Resistance
Current Drug Metabolism Preclinical and Clinical Studies on the Use of Platinum Complexes for Breast Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Assessment of Nutritional Status in Cancer – The Relationship Between Body Composition and Pharmacokinetics
Anti-Cancer Agents in Medicinal Chemistry TGF-β Pathway as a Therapeutic Target in Bone Metastases
Current Pharmaceutical Design Target-oriented Mechanisms of Novel Herbal Therapeutics in the Chemotherapy of Gastrointestinal Cancer and Inflammation
Current Pharmaceutical Design Prostaglandins Pathway as a Possible Biological Link Between Cancer and Major Depression
Current Angiogenesis (Discontinued)