Abstract
Retinoids play a crucial role in cellular differentiation and proliferation of epithelial tissue and their utility in oncology and dermatology is well documented. This mini review focuses on the role of all-trans-retinoic acid (ATRA or RA), the principal endogenous retinoid and its metabolism in cancer therapy. ATRA has been used successfully in differentiating therapy of acute promyelecytic leukemia and other types of cancers. However, its usefulness is limited by the rapid emergence of ATRA resistance due (in part) to ATRA - induced acceleration of ATRA metabolism. A novel strategy to subjugate the limitation associated with exogenous ATRA therapy has been to modulate and / or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzyme(s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs). This review highlights development in the design, synthesis and evaluation of RAMBAs since 1987. Major emphasis is given to liarozole, the most studied and only RAMBA to undergo clinical investigation and also the recently developed novel and highly potent 4-azoly retinoids. The potential role of a new family of cytochrome P450 enzymes, CYP26, with specificity towards ATRA is also discussed.
Keywords: liarozole, atra-hydroxylase inhibitor, rambas, 4-azoye retinoids
Mini-Reviews in Medicinal Chemistry
Title: Cytochrome P450 Retinoic Acid 4-Hydroxylase Inhibitors: Potential Agents for Cancer Therapy
Volume: 2 Issue: 3
Author(s): V. C.O. Njar
Affiliation:
Keywords: liarozole, atra-hydroxylase inhibitor, rambas, 4-azoye retinoids
Abstract: Retinoids play a crucial role in cellular differentiation and proliferation of epithelial tissue and their utility in oncology and dermatology is well documented. This mini review focuses on the role of all-trans-retinoic acid (ATRA or RA), the principal endogenous retinoid and its metabolism in cancer therapy. ATRA has been used successfully in differentiating therapy of acute promyelecytic leukemia and other types of cancers. However, its usefulness is limited by the rapid emergence of ATRA resistance due (in part) to ATRA - induced acceleration of ATRA metabolism. A novel strategy to subjugate the limitation associated with exogenous ATRA therapy has been to modulate and / or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzyme(s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs). This review highlights development in the design, synthesis and evaluation of RAMBAs since 1987. Major emphasis is given to liarozole, the most studied and only RAMBA to undergo clinical investigation and also the recently developed novel and highly potent 4-azoly retinoids. The potential role of a new family of cytochrome P450 enzymes, CYP26, with specificity towards ATRA is also discussed.
Export Options
About this article
Cite this article as:
Njar C.O. V., Cytochrome P450 Retinoic Acid 4-Hydroxylase Inhibitors: Potential Agents for Cancer Therapy, Mini-Reviews in Medicinal Chemistry 2002; 2 (3) . https://dx.doi.org/10.2174/1389557023406223
DOI https://dx.doi.org/10.2174/1389557023406223 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
Related Articles
-
Vasoproliferation and Antiproliferative Treatment Options in Pulmonary Arterial Hypertension
Recent Patents on Cardiovascular Drug Discovery Update on MDS Therapy: From Famine to Feast
Cardiovascular & Hematological Agents in Medicinal Chemistry Targeting of Adhesion Molecules as a Therapeutic Strategy in Multiple Myeloma
Current Cancer Drug Targets Overview of Tumor-Associated Antigens (TAAs) as Potential Therapeutic Targets for Prostate Cancer Therapy
Current Cancer Therapy Reviews P-glycoprotein Inhibition: The Past, the Present and the Future
Current Drug Metabolism Clinical Trials of Targeted Alpha Therapy for Cancer
Reviews on Recent Clinical Trials An Update on Clinical Drug Interactions with the Herbal Antidepressant St. Johns wort
Current Drug Metabolism CAR T-cell Therapy: A New Era in Cancer Immunotherapy
Current Pharmaceutical Biotechnology Pro-inflammatory Cytokines in Animal and Human Gestation
Current Pharmaceutical Design Improving Safety of Gene Therapy
Current Drug Safety Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis
Current Drug Metabolism Monoclonal Antibody Therapy in Haematological Malignancies
Current Clinical Pharmacology Theoretical Analysis for the Safe Form and Dosage of Amygdalin Product
Anti-Cancer Agents in Medicinal Chemistry N6-Methyladenosine-Related RNA Signature Predicting the Prognosis of Ovarian Cancer
Recent Patents on Anti-Cancer Drug Discovery Trends in Cell-Based Electrochemical Biosensors
Current Medicinal Chemistry Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Receptor Tyrosine Kinases: The Main Targets for New Anticancer Therapy
Current Drug Targets Role of Growth Factors in the Pathogenesis of Tissue Fibrosis in Systemic Sclerosis
Current Rheumatology Reviews CFTR and MDR: ABC Transporters with Homologous Structure but Divergent Function
Current Genomics ABC Transporter Inhibitors in Reversing Multidrug Resistance to Chemotherapy
Current Drug Targets