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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Inflammation in Ischemic Stroke Subtypes
Current Pharmaceutical Design Advances in the Researches on the Biological Activities and Inhibitors of Phosphatidylinositol 3-kinase
Anti-Cancer Agents in Medicinal Chemistry Natural Antibodies: Protecting Role of IgM in Glioblastoma and Brain Tumours
Current Pharmaceutical Design Novel Classes of Dimer Antitumour Drug Candidates
Current Pharmaceutical Design Defining the Role of Integrin αvβ6 in Cancer
Current Drug Targets Angiogenesis and Vascularization of Uterine Leiomyoma: Clinical Value of Pseudocapsule Containing Peptides and Neurotransmitters
Current Protein & Peptide Science 2,3-Dichloro-1,4-Naphthoquinone in Organic Synthesis: Recent Advances
Mini-Reviews in Organic Chemistry Relaxin Receptors - New Drug Targets for Multiple Disease States
Current Drug Targets Anti-Tubercular and Anti-Inflammatory Activities of Azetidin-2-One Derivatives and Their Effects on the Activity of Phospholipase A2
Medicinal Chemistry Resistance to Radiotherapy and Targeted Molecular Therapies in Squamous Cell Carcinomas of the Head and Neck, Preclinical Data and New Approaches
Current Signal Transduction Therapy Intersection of MicroRNA and Gene Regulatory Networks and their Implication in Cancer
Current Pharmaceutical Biotechnology Topical Use of Sucralfate in Epithelial Wound Healing: Clinical Evidence and Molecular Mechanisms of Action
Recent Patents on Inflammation & Allergy Drug Discovery Editorial [Hot Topic: Diagnostic and Therapeutic Optical Imaging Techniques]
Current Medical Imaging Phytochemical Screening, Antiproliferative and Antioxidant Properties of Various Extracts from Endemic Origanum acutidens
Combinatorial Chemistry & High Throughput Screening Application of Molecular Diagnostics to the Evaluation of the Surgical Approach to Thyroid Cancer
Current Genomics The Anticancer Properties of Dietary Polyphenols and its Relation with Apoptosis
Current Pharmaceutical Design Subject Index To Volume 6
Current Molecular Medicine Metformin Protects the Brain Against the Oxidative Imbalance Promoted by Type 2 Diabetes
Medicinal Chemistry Is Senescence Reversible?
Current Drug Targets From Natural Products to Designer Drugs: Development and Molecular Mechanisms Action of Novel Anti-Microtubule Breast Cancer Therapeutics
Current Topics in Medicinal Chemistry