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
-
Next Generation Tyrosine Kinase Inhibitor (TKI): Afatinib
Recent Patents on Anti-Cancer Drug Discovery Growth Retardation in Children with Celiac Disease
Current Pediatric Reviews DNA-Damaging Anticancer Drugs – A Perspective for DNA Repair- Oriented Therapy
Current Medicinal Chemistry Targeting BMP9-Promoted Human Osteosarcoma Growth by Inactivation of Notch Signaling
Current Cancer Drug Targets Gemini Surfactant Based Carriers in Gene and Drug Delivery
Current Medicinal Chemistry Template Dependent Human DNA Polymerases
Current Topics in Medicinal Chemistry Inflammation as Therapeutic Objective in Stroke
Current Pharmaceutical Design Targeting PDK1 in Cancer
Current Medicinal Chemistry Endocrine and Antineoplastic Actions of Growth Hormone-Releasing Hormone Antagonists
Current Medicinal Chemistry The Ambivalent Role of Apoptosis in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
Current Pharmaceutical Design Combinatorial Nanoparticles for Cancer Diagnosis and Therapy
Current Medicinal Chemistry Evaluation of Fourteen Aurone Derivatives as Potential Anti-Cancer Agents
Current Pharmaceutical Biotechnology Genetic Polymorphisms and Haplotypes of Major Drug Metabolizing Enzymes in East Asians and Their Comparison with Other Ethnic Populations
Current Pharmacogenomics Fibroblast Growth Factors in Development and Cancer: Insights from the Mammary and Prostate Glands
Current Drug Targets Detection and Therapeutic Implications of c-Met Mutations in Small Cell Lung Cancer and Neuroendocrine Tumors
Current Pharmaceutical Design Eph Receptor Tyrosine Kinases in Tumor and Tumor Microenvironment
Current Pharmaceutical Design Notch Signalling Pathways and Their Importance in the Treatment of Cancers
Current Drug Targets H3K4 Methylation Status and Lysine Specific Methyltransferase KMT2C Expression Correlate with Prognosis in Lung Adenocarcinoma
Current Molecular Pharmacology Chemoradiotherapy of Human Tumors: Novel Approaches from Nanomedicine
Current Pharmaceutical Design Ribozymes in the Age of Molecular Therapeutics
Current Molecular Medicine