Abstract
Carcinogenesis of hormone-related cancers involves hormone-stimulated cell proliferation, which increases the number of cell divisions and the opportunity for random genetic errors. In target tissues, steroid hormones are interconverted between their potent, high affinity forms for their respective receptors and their inactive, low affinity forms. One group of enzymes responsible for these interconversions are the hydroxysteroid dehydrogenases, which regulate ligand access to steroid receptors and thus act at a pre-receptor level. As part of this group, the 17β-hydroxysteroid dehydrogenases catalyze either oxidation of hydroxyl groups or reduction of keto groups at steroid position C17. The thoroughly characterized 17β-hydroxysteroid dehydrogenase type 1 activates the less active estrone to estradiol, a potent ligand for estrogen receptors. This isoform is expressed in gonads, where it affects circulating levels of estradiol, and in peripheral tissue, where it regulates ligand occupancy of estrogen receptors. Inhibitors of 17β-hydroxysteroid dehydrogenase type 1 are thus highly interesting potential therapeutic agents for the control of estrogen-dependent diseases such as endometriosis, as well as breast and ovarian cancers. Here, we present the review on the recent development of inhibitors of 17β-hydroxysteroid dehydrogenase type 1 published and patented since the previous review of 17β-hydroxysteroid dehydrogenase inhibitors of Poirier (Curr. Med. Chem., 2003, 10, 453). These inhibitors are divided into two separate groups according to their chemical structures: steroidal and non-steroidal 17β- hydroxysteroid dehydrogenase type 1 inhibitors. Their estrogenic/ proliferative activities and selectivities over other 17β-hydroxysteroid dehydrogenases that are involved in local regulation of estrogen action (types 2, 7 and 12) are also presented.
Keywords: 17β-hydroxysteroid dehydrogenase type 1, inhibitors, drugs, steroids
Current Medicinal Chemistry
Title: Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1
Volume: 15 Issue: 2
Author(s): S. Gobec, P. Brozic and T. Lanisnik Rizner
Affiliation:
Keywords: 17β-hydroxysteroid dehydrogenase type 1, inhibitors, drugs, steroids
Abstract: Carcinogenesis of hormone-related cancers involves hormone-stimulated cell proliferation, which increases the number of cell divisions and the opportunity for random genetic errors. In target tissues, steroid hormones are interconverted between their potent, high affinity forms for their respective receptors and their inactive, low affinity forms. One group of enzymes responsible for these interconversions are the hydroxysteroid dehydrogenases, which regulate ligand access to steroid receptors and thus act at a pre-receptor level. As part of this group, the 17β-hydroxysteroid dehydrogenases catalyze either oxidation of hydroxyl groups or reduction of keto groups at steroid position C17. The thoroughly characterized 17β-hydroxysteroid dehydrogenase type 1 activates the less active estrone to estradiol, a potent ligand for estrogen receptors. This isoform is expressed in gonads, where it affects circulating levels of estradiol, and in peripheral tissue, where it regulates ligand occupancy of estrogen receptors. Inhibitors of 17β-hydroxysteroid dehydrogenase type 1 are thus highly interesting potential therapeutic agents for the control of estrogen-dependent diseases such as endometriosis, as well as breast and ovarian cancers. Here, we present the review on the recent development of inhibitors of 17β-hydroxysteroid dehydrogenase type 1 published and patented since the previous review of 17β-hydroxysteroid dehydrogenase inhibitors of Poirier (Curr. Med. Chem., 2003, 10, 453). These inhibitors are divided into two separate groups according to their chemical structures: steroidal and non-steroidal 17β- hydroxysteroid dehydrogenase type 1 inhibitors. Their estrogenic/ proliferative activities and selectivities over other 17β-hydroxysteroid dehydrogenases that are involved in local regulation of estrogen action (types 2, 7 and 12) are also presented.
Export Options
About this article
Cite this article as:
Gobec S., Brozic P. and Rizner Lanisnik T., Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1, Current Medicinal Chemistry 2008; 15 (2) . https://dx.doi.org/10.2174/092986708783330629
DOI https://dx.doi.org/10.2174/092986708783330629 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Synthesis, Cytotoxic Evaluation, and Molecular Docking Studies of New Oxadiazole Analogues
Letters in Organic Chemistry Tyrosine Kinase Inhibitors
Current Cancer Drug Targets Therapeutic and Diagnostic Agents based on Bioactive Endogenous and Exogenous Coordination Compounds
Current Medicinal Chemistry Stopping Cancer in its Tracks: Using Small Molecular Inhibitors to Target Glioblastoma Migrating Cells
Current Drug Discovery Technologies Oxaliplatin-mediated Inhibition of Survivin Increases Sensitivity of Head and Neck Squamous Cell Carcinoma Cell Lines to Paclitaxel
Current Cancer Drug Targets Cytostatic and Apoptotic Effects of DNMT and HDAC Inhibitors in Endometrial Cancer Cells
Current Pharmaceutical Design Roles of Nuclear Receptors in Esophageal Cancer
Current Pharmaceutical Biotechnology Artemisinin Attenuates Isoproterenol-induced Cardiac Hypertrophy via the ERK1/2 and p38 MAPK Signaling Pathways
Current Molecular Pharmacology The Role, Significance, and Association of MicroRNA-10a/b in Physiology of Cancer
MicroRNA MUC1 Story: Great Expectations, Disappointments and the Renaissance
Current Medicinal Chemistry Design, Synthesis and Biological Evaluation of 5-Amino-1H-pyrazole-4- carboxamide Derivatives as Potential Antitumor Agents
Letters in Drug Design & Discovery Effects of Adjuvant Chelator or Chemotherapy on Dosimetry of 90Y-CC49 in Lung Cancer Patients Using 111In-CC49 as a Tracer
Drug Design Reviews - Online (Discontinued) Hepatocellular Carcinoma Detection by Gallium Scan and Subsequent Treatment by Gallium Maltolate: Rationale and Case Study
Anti-Cancer Agents in Medicinal Chemistry Oocyte Cryopreservation for Elective Preservation of Reproductive Potential
Current Women`s Health Reviews Anti-Metastatics: An Overview of Drug Candidates in Current Pipelines
Current Pharmaceutical Design Iron Oxide Nanoparticles: An Insight into their Biomedical Applications
Current Medicinal Chemistry Rapid Desensitization of Hypersensitivity Reactions to Chemotherapy Agents.
Current Drug Safety Advances on Magnetic Nanocarriers Based on Natural Polymers
Current Pharmaceutical Design A Novel Oncogenic Role of Disulfidptosis-related Gene SLC7A11 in Anti-tumor Immunotherapy Response to Human Cancers
Current Cancer Drug Targets Platinum-Based Agents for Individualized Cancer Treatment
Current Molecular Medicine