Abstract
All-trans retinoic acid (atRA) is the transcriptionally active product of vitamin A and induces gene expression via specific receptors at nM concentrations. Essential enzymes that regulate the local levels of atRA are the CYP26 members of the cytochrome P450 family, which catabolize atRA. Compounds that have been designed to inhibit these enzymes are known as Retinoic Acid Metabolic Blocking Agents (RAMBAs). Treatment with these compounds will raise endogenous atRA levels and may be therapeutic for the treatment of diseases that respond to high atRA concentrations, including several types of cancer as well as skin conditions such as psoriasis and acne. This review describes the mechanism of action of the RAMBAs and discusses the potential side effects of these compounds. atRA is highly teratogenic and the potential teratogenicity of the RAMBAs is described by comparison with the abnormalities resulting from null mutation of individual CYP26 genes. The possible effects of RAMBAs on the adult brain are also described that have the potential for harm but, in the right circumstances, may also be beneficial.
Keywords: Retinoic acid, CYP26, catabolism, caudal regression, limb defect, neurogenesis, hippocampus
Current Pharmaceutical Design
Title: Prospective Teratology of Retinoic Acid Metabolic Blocking Agents (RAMBAs) and Loss of CYP26 Activity
Volume: 13 Issue: 29
Author(s): P. McCaffery and C. Simons
Affiliation:
Keywords: Retinoic acid, CYP26, catabolism, caudal regression, limb defect, neurogenesis, hippocampus
Abstract: All-trans retinoic acid (atRA) is the transcriptionally active product of vitamin A and induces gene expression via specific receptors at nM concentrations. Essential enzymes that regulate the local levels of atRA are the CYP26 members of the cytochrome P450 family, which catabolize atRA. Compounds that have been designed to inhibit these enzymes are known as Retinoic Acid Metabolic Blocking Agents (RAMBAs). Treatment with these compounds will raise endogenous atRA levels and may be therapeutic for the treatment of diseases that respond to high atRA concentrations, including several types of cancer as well as skin conditions such as psoriasis and acne. This review describes the mechanism of action of the RAMBAs and discusses the potential side effects of these compounds. atRA is highly teratogenic and the potential teratogenicity of the RAMBAs is described by comparison with the abnormalities resulting from null mutation of individual CYP26 genes. The possible effects of RAMBAs on the adult brain are also described that have the potential for harm but, in the right circumstances, may also be beneficial.
Export Options
About this article
Cite this article as:
McCaffery P. and Simons C., Prospective Teratology of Retinoic Acid Metabolic Blocking Agents (RAMBAs) and Loss of CYP26 Activity, Current Pharmaceutical Design 2007; 13 (29) . https://dx.doi.org/10.2174/138161207782110534
DOI https://dx.doi.org/10.2174/138161207782110534 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Morphological Based Medical Image Processing on Cervical Cytology Cancer
Images Using Connected Component Techniques
Current Medical Imaging Design of Oleanolic Acid-based Hybrid Compounds as Potential Pharmaceutical Scaffolds
Letters in Drug Design & Discovery Discovery of New Biomarkers of Cancer Using Proteomics Technology
Current Cancer Therapy Reviews The Origin and Identification of Mesenchymal Stem Cells in Teeth: from Odontogenic to Non-odontogenic
Current Stem Cell Research & Therapy Formation of Five- and Six-Membered α,β-Unsaturated Lactones through Ring- Closing Metathesis of Functionalized Acrylates. Applications to Synthesis of Natural Products
Current Organic Chemistry Resveratrol, a Phytochemical Inducer of Multiple Cell Death Pathways: Apoptosis, Autophagy and Mitotic Catastrophe
Current Medicinal Chemistry Dendritic Cell Immunotherapy for Malignant Gliomas
Reviews on Recent Clinical Trials Recent Updates on <i>Sinularia</i> Soft Coral
Mini-Reviews in Medicinal Chemistry T Cell Replicative Senescence in Human Aging
Current Pharmaceutical Design Nano Traditional Chinese Medicine: Current Progresses and Future Challenges
Current Drug Targets Base Excision Repair: Contribution to Tumorigenesis and Target in Anticancer Treatment Paradigms
Current Medicinal Chemistry Mucosal Vaccines: Where Do We Stand?
Current Topics in Medicinal Chemistry Selective Inhibitors of Zinc-Dependent Histone Deacetylases. Therapeutic Targets Relevant to Cancer
Current Pharmaceutical Design 6-Bromo-2,3-Dioxoindolin Phenylacetamide Derivatives: Synthesis, Potent CDC25B, PTP1B Inhibitors and Anticancer Activity
Letters in Drug Design & Discovery Anticancer Antioxidant Regulatory Functions of Phytochemicals
Current Medicinal Chemistry Endometriosis and Gynecological Cancer
Current Women`s Health Reviews Methionine Aminopeptidases as Potential Targets for Treatment of Gastrointestinal Cancers and other Tumors
Current Drug Targets Triterpenoids for Cancer Prevention and Treatment: Current Status and Future Prospects
Current Pharmaceutical Biotechnology Epigenetic Mechanism Involved in the HBV/HCV-Related Hepatocellular Carcinoma Tumorigenesis
Current Pharmaceutical Design Cancer Drug Development Using Glucose Metabolism Radiopharmaceuticals
Current Pharmaceutical Design