Abstract
In this review the preclinical medicinal chemistry, biochemistry and clinical results achieved in the treatment of prostatic disease with dutasteride, a dual inhibitor of type 1 and type 2 5α-reductase are described. During the discovery phase, dutasteride was optimized to inhibit both forms of human 5 α-reductase (5AR) via extensive structure activity relationship studies versus the cloned human isozymes. Dutasteride has subsequently been shown to improve disease measures in patients with symptomatic benign prostatic hyperplasia (BPH) in three randomized, placebo-controlled, Phase III clinical studies lasting for 2 years. Additionally, dutasteride is now under study for the ability to reduce the incidence of prostate cancer in men at high risk of the disease - an indication where the unique dual inhibitor nature, half-life and tolerability of dutasteride may be especially significant factors in determining treatment success. The connections between preclinical drug design and clinical outcomes during the discovery and development of dutasteride are exemplified.
Keywords: dihydrofinasteride-NADP adduct, 5AR isozymes, Vermeulen, progesterone, prostate cDNA library
Current Topics in Medicinal Chemistry
Title: Discovery and Clinical Development of Dutasteride, a Potent Dual 5α- Reductase Inhibitor
Volume: 6 Issue: 5
Author(s): Stephen V. Frye
Affiliation:
Keywords: dihydrofinasteride-NADP adduct, 5AR isozymes, Vermeulen, progesterone, prostate cDNA library
Abstract: In this review the preclinical medicinal chemistry, biochemistry and clinical results achieved in the treatment of prostatic disease with dutasteride, a dual inhibitor of type 1 and type 2 5α-reductase are described. During the discovery phase, dutasteride was optimized to inhibit both forms of human 5 α-reductase (5AR) via extensive structure activity relationship studies versus the cloned human isozymes. Dutasteride has subsequently been shown to improve disease measures in patients with symptomatic benign prostatic hyperplasia (BPH) in three randomized, placebo-controlled, Phase III clinical studies lasting for 2 years. Additionally, dutasteride is now under study for the ability to reduce the incidence of prostate cancer in men at high risk of the disease - an indication where the unique dual inhibitor nature, half-life and tolerability of dutasteride may be especially significant factors in determining treatment success. The connections between preclinical drug design and clinical outcomes during the discovery and development of dutasteride are exemplified.
Export Options
About this article
Cite this article as:
Frye V. Stephen, Discovery and Clinical Development of Dutasteride, a Potent Dual 5α- Reductase Inhibitor, Current Topics in Medicinal Chemistry 2006; 6 (5) . https://dx.doi.org/10.2174/156802606776743101
DOI https://dx.doi.org/10.2174/156802606776743101 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- 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
-
Effects of Iron Chelation in Osteosarcoma
Current Cancer Drug Targets Molecular Chaperones as Rational Drug Targets for Parkinsons Disease Therapeutics
CNS & Neurological Disorders - Drug Targets Recent Patents Relating to Tumor Suppressor Genes
Recent Patents on DNA & Gene Sequences Radiolabeled GRPR Antagonists for Imaging of Disseminated Prostate Cancer - Influence of Labeling Chemistry on Targeting Properties
Current Medicinal Chemistry Withdrawal Notice: Emerging Biomarkers and Contributing Factors of Prostate Cancer
Current Cancer Therapy Reviews Tumor Protein p63/microRNA Network in Epithelial Cancer Cells
Current Genomics Phytochemical, Anti-diabetic and Cardiovascular Properties of Urtica dioica L. (Urticaceae): A Review
Mini-Reviews in Medicinal Chemistry Therapeutic Targeting of Apoptotic Pathways in Cancer
Current Drug Targets Editorial [Hot topic: Current Topics in the Development of Radioligands for Positron-Emission Tomography Imaging (Guest Editors: Andrew G. Horti and Robert F. Dannals)]
Current Topics in Medicinal Chemistry STAT3 Activation in Circulating Monocytes Contributes to Neovascular Age-Related Macular Degeneration
Current Molecular Medicine MDM2 Inhibitors for Pancreatic Cancer Therapy
Mini-Reviews in Medicinal Chemistry Inflammatory and Neurodegenerative Pathways in Depression: A New Avenue for Antidepressant Development?
Current Medicinal Chemistry Glioma: Tryptophan Catabolite and Melatoninergic Pathways Link microRNA, 14-3- 3, Chromosome 4q35, Epigenetic Processes and other Glioma Biochemical Changes
Current Pharmaceutical Design Selenium in the Therapy of Neurological Diseases. Where is it Going?
Current Neuropharmacology Cardiovascular Molecular Imaging: New Methodological Strategies
Current Pharmaceutical Design Post-Translational Modifications of PTEN and their Potential Therapeutic Implications
Current Cancer Drug Targets The Possibility of Preventive and Therapeutic Use of Green Tea Catechins in Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry Reactive Oxygen Species, Cancer and Anti-Cancer Therapies
Current Chemical Biology Bioinformatics Tools for Mass Spectrometry-Based High-Throughput Quantitative Proteomics Platforms
Current Proteomics The Canadian Biomarker Integration Network in Depression (CAN-BIND): Advances in Response Prediction
Current Pharmaceutical Design