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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
4-Methylumbelliferones Analogues as Anticancer Agents: Synthesis and in Cell Pharmacological Studies
Anti-Cancer Agents in Medicinal Chemistry An Emerging Molecular Target in Melanoma: Cellular Carbonyl Stress and the Inhibition of Mitochondrial Survival Pathways by Carbonyl Scavenger Agents
Current Cancer Therapy Reviews Functions of S100 Proteins
Current Molecular Medicine History and Evolution of Reproductive and Developmental Toxicology Guidelines
Current Pharmaceutical Design Controlled Gene Delivery Can Enhance Therapeutic Outcome for Cancer Immune Therapy for Melanoma
Current Gene Therapy The Hypothalamic-Pituitary-Adrenal Axis: What can it Tell us About Stressors?
CNS & Neurological Disorders - Drug Targets Signal Transduction Therapy for Cancer - Whither Now?
Current Signal Transduction Therapy Neuroimmune Aspects of Sjogren`s Syndrome: Role of VIP/VPAC System in Immune and Salivary Gland Epithelial Cell Function
Current Pharmaceutical Design Advances in Molecular Therapeutic Approaches to Patients with Malignant Gliomas
Current Signal Transduction Therapy Sunlight Vitamin D and Skin Cancer
Anti-Cancer Agents in Medicinal Chemistry Anti-inflammatory, Antioxidant and Antiproliferative Activities from Trichilia silvatica (C.DC)
Current Pharmaceutical Biotechnology Genes that Modulate the Sensitivity for Anti-Microtubule Drug-Mediated Chemotherapy
Current Cancer Drug Targets Opioids Resistance in Chronic Pain Management
Current Neuropharmacology Chemotherapeutic Effects of Acridine Derivatives
Medicinal Chemistry Reviews - Online (Discontinued) Pharmacological Properties of Thalidomide and its Analogues
Recent Patents on Inflammation & Allergy Drug Discovery The Use of SIFT-MS in Profiling the Faecal Volatile Metabolome in Horses with Colic: A Pilot Study
Current Analytical Chemistry Antisense Technology: A Selective Tool for Gene Expression Regulation and Gene Targeting
Current Pharmaceutical Biotechnology AMPK: Therapeutic Target for Diabetes and Cancer Prevention
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Organic Synthesis Therapeutic Polycomb Targeting in Human Cancer
Recent Patents on Regenerative Medicine