Abstract
Cytochrome P450 (CYP) enzymes are a superfamily of heme containing proteins that catalyze xenobiotic metabolism phase I reactions. Oxidation reactions are the most common CYP-catalyzed reactions for both endogenous substrates and exogenous compounds, including drugs, although CYP enzymes are capable also to catalyze reduction reactions. Whereas the majority of clinically used drugs are inactivated by CYPs, several prodrugs are bioconverted to their active species by these enzymes. Therefore, this mechanism could be exploited to a greater extend, e.g. by taking advantage of the different CYP enzymes to achieve targeted drug delivery, to improve efficacy or to decrease the unwanted adverse effects of existing and novel drug molecules. This review describes the potential of CYP enzymes in prodrug design and summarizes a wide variety of CYP-activated prodrug structures, which are on the market or under the development. The bioactivation mechanisms of each CYP-activated prodrug structure are described and the specificity for the different forms of CYP enzymes is discussed.
Keywords: Antibody-directed enzyme prodrug therapy (ADEPT), cyclic phosphate, cytochrome P450 enzyme, gene-directed enzyme prodrug therapy (GDEPT), N-oxide, nucleoside, oxazaphosphorine, oxime, prodrug, targeted drug delivery
Current Medicinal Chemistry
Title: Cytochrome P450-Activated Prodrugs: Targeted Drug Delivery
Volume: 15 Issue: 23
Author(s): Kristiina M. Huttunen, Niina Mahonen, Hannu Raunio and Jarkko Rautio
Affiliation:
Keywords: Antibody-directed enzyme prodrug therapy (ADEPT), cyclic phosphate, cytochrome P450 enzyme, gene-directed enzyme prodrug therapy (GDEPT), N-oxide, nucleoside, oxazaphosphorine, oxime, prodrug, targeted drug delivery
Abstract: Cytochrome P450 (CYP) enzymes are a superfamily of heme containing proteins that catalyze xenobiotic metabolism phase I reactions. Oxidation reactions are the most common CYP-catalyzed reactions for both endogenous substrates and exogenous compounds, including drugs, although CYP enzymes are capable also to catalyze reduction reactions. Whereas the majority of clinically used drugs are inactivated by CYPs, several prodrugs are bioconverted to their active species by these enzymes. Therefore, this mechanism could be exploited to a greater extend, e.g. by taking advantage of the different CYP enzymes to achieve targeted drug delivery, to improve efficacy or to decrease the unwanted adverse effects of existing and novel drug molecules. This review describes the potential of CYP enzymes in prodrug design and summarizes a wide variety of CYP-activated prodrug structures, which are on the market or under the development. The bioactivation mechanisms of each CYP-activated prodrug structure are described and the specificity for the different forms of CYP enzymes is discussed.
Export Options
About this article
Cite this article as:
Huttunen M. Kristiina, Mahonen Niina, Raunio Hannu and Rautio Jarkko, Cytochrome P450-Activated Prodrugs: Targeted Drug Delivery, Current Medicinal Chemistry 2008; 15 (23) . https://dx.doi.org/10.2174/092986708785909120
DOI https://dx.doi.org/10.2174/092986708785909120 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Cytokines and Chemokines as Regulators of Angiogenesis in Health and Disease
Current Pharmaceutical Design Discovery of Cationic Polymers for Non-Viral Gene Delivery Using Combinatorial Approaches
Combinatorial Chemistry & High Throughput Screening Bortezomib as the First Proteasome Inhibitor Anticancer Drug: Current Status and Future Perspectives
Current Cancer Drug Targets Molecular Markers of Tumor Progression in Melanoma
Current Genomics Gene Electrotransfer: A Mechanistic Perspective
Current Gene Therapy Bcl-2 Family Proteins as Therapeutic Targets
Current Pharmaceutical Design The Hepatocyte Growth Factor Receptor: Structure, Function and Pharmacological Targeting in Cancer
Current Signal Transduction Therapy Curcumin Targets Circulating Cancer Stem Cells by Inhibiting Self-Renewal Efficacy in Non-Small Cell Lung Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Targeted Therapies in Combination with Radiotherapy in Oesophageal and Gastroesophageal Carcinoma
Current Medicinal Chemistry What is Currently the Best Radiopharmaceutical for the Hybrid PET/CT Detection of Recurrent Medullary Thyroid Carcinoma?
Current Radiopharmaceuticals Eliminating Ovarian Cancer Stem Cells: A Potential Therapeutic Target for Ovarian Cancer Chemoresistance
Current Protein & Peptide Science Transglutaminase-Mediated Activation of Nuclear Transcription Factor-κB in Cancer Cells: A New Therapeutic Opportunity
Current Cancer Drug Targets Injectable Thermosensitive Chitosan/Glycerophosphate-Based Hydrogels for Tissue Engineering and Drug Delivery Applications: A Review
Recent Patents on Drug Delivery & Formulation The Place of Somatostatin Analogs in the Diagnosis and Treatment of the Neuoroendocrine Glands Tumors
Recent Patents on Anti-Cancer Drug Discovery The Diversity of Epithelial Secreted Mucins
Current Organic Chemistry Clinical Approaches Toward Tumor Angiogenesis: Past, Present and Future
Current Pharmaceutical Design The Potential of Natural Products as Effective Treatments for Allergic Inflammation: Implications for Allergic Rhinitis
Current Topics in Medicinal Chemistry Genetics and Genomics of Hepatic Acute Phase Reactants: A Mini-Review
Inflammation & Allergy - Drug Targets (Discontinued) Strategy of Cancer Targeting Gene-Viro-Therapy (CTGVT) a Trend in Both Cancer Gene Therapy and Cancer Virotherapy
Current Pharmaceutical Biotechnology Neurological Involvement in Rheumatoid Arthritis
Current Immunology Reviews (Discontinued)