Abstract
A high proportion (∼40%) of breast cancers are hormone-dependent and it is the female hormone estradiol (E2) that is believed to play a key role in the initiation, promotion and progression of this disease. In the fight against this disease, compounds which are potent inhibitors of the cytochrome P-450 enzyme aromatase (AR) (which catalyses the conversion of the C19 androgens to the C18 estrogens) have been the major target. However, the administration of AR inhibitors alone does not prevent the localised biosynthesis of estrone (E1) (and therefore the subsequent synthesis of E2) within breast tumour cells via alternative non-AR routes. This has therefore been the major impetus for the development of steroid sulfatase (E1STS) inhibitors. The E1STS enzyme regulates the formation of E1 from estrone sulfate (E1S), a steroid conjugate present in high concentrations in tissue and blood in women with breast cancer. The STS enzyme has also been shown to catalyse the formation of dehydroepiandrosterone (DHEA) from DHEA-sulfate (DHEAS). This is important since DHEA can be converted to 5-androstene-3β,17β-diol, which has been shown to possess weak estrogenic properties, however, due to the high concentration of this steroid, it is able to stimulate the growth of breast cancer cells in vitro and in vivo. Considerable progress has been made in recent years in the development of a number of potent E1STS inhibitors, as such both steroidal and non-steroidal compounds have been considered and a number of highly potent inhibitors have been produced and evaluated against what is now considered a crucial enzyme in the fight against hormone-dependent breast cancer. The review therefore summarises the work that has been undertaken todate.
Anti-Cancer Agents in Medicinal Chemistry
Title: Estrone Sulfatase and Its Inhibitors
Volume: 9 Issue: 6
Author(s): Kwabina Aidoo-Gyamfi, Tim Cartledge, Kruti Shah and Sabbir Ahmed
Affiliation:
Abstract: A high proportion (∼40%) of breast cancers are hormone-dependent and it is the female hormone estradiol (E2) that is believed to play a key role in the initiation, promotion and progression of this disease. In the fight against this disease, compounds which are potent inhibitors of the cytochrome P-450 enzyme aromatase (AR) (which catalyses the conversion of the C19 androgens to the C18 estrogens) have been the major target. However, the administration of AR inhibitors alone does not prevent the localised biosynthesis of estrone (E1) (and therefore the subsequent synthesis of E2) within breast tumour cells via alternative non-AR routes. This has therefore been the major impetus for the development of steroid sulfatase (E1STS) inhibitors. The E1STS enzyme regulates the formation of E1 from estrone sulfate (E1S), a steroid conjugate present in high concentrations in tissue and blood in women with breast cancer. The STS enzyme has also been shown to catalyse the formation of dehydroepiandrosterone (DHEA) from DHEA-sulfate (DHEAS). This is important since DHEA can be converted to 5-androstene-3β,17β-diol, which has been shown to possess weak estrogenic properties, however, due to the high concentration of this steroid, it is able to stimulate the growth of breast cancer cells in vitro and in vivo. Considerable progress has been made in recent years in the development of a number of potent E1STS inhibitors, as such both steroidal and non-steroidal compounds have been considered and a number of highly potent inhibitors have been produced and evaluated against what is now considered a crucial enzyme in the fight against hormone-dependent breast cancer. The review therefore summarises the work that has been undertaken todate.
Export Options
About this article
Cite this article as:
Aidoo-Gyamfi Kwabina, Cartledge Tim, Shah Kruti and Ahmed Sabbir, Estrone Sulfatase and Its Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (6) . https://dx.doi.org/10.2174/187152009788679985
DOI https://dx.doi.org/10.2174/187152009788679985 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis
Current Neuropharmacology Tumor Specific Novel Taxoid-Monoclonal Antibody Conjugates
Current Medicinal Chemistry Dual Roles of Sulforaphane in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Deubiquitinating Enzymes as Therapeutic Targets in Cancer
Current Pharmaceutical Design Radiopharmaceuticals for Oncology Drug Development: A Pharmaceutical Industry Perspective
Current Pharmaceutical Design STAT3 as a Therapeutic Target for Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Malignancy in Common Variable Immune Deficiency: Report of Two Rare Cases of Gastrointestinal Malignancy and a Review of the Literature
Cardiovascular & Hematological Disorders-Drug Targets Review: The Role of Radiolabeled DOTA-Conjugated Peptides for Imaging and Treatment of Childhood Neuroblastoma
Current Radiopharmaceuticals STAT3 Regulation of Glioblastoma Pathogenesis
Current Molecular Medicine Antisense Oligonucleotides in the Treatment of Cerebral Gliomas. Review of Concerning Patents
Recent Patents on CNS Drug Discovery (Discontinued) Vascular Endothelial Growth Factor (VEGF) as a Target of Bevacizumab in Cancer: From the Biology to the Clinic
Current Medicinal Chemistry Liposomes and Lipid Envelope-Type Systems for Systemic siRNA Delivery
Current Pharmaceutical Design Betulinic Acid as a Potent and Complex Antitumor Phytochemical: A Minireview
Anti-Cancer Agents in Medicinal Chemistry Design of multifunctional nanocarriers for delivery of anti-cancer therapy
Current Pharmaceutical Design Pyrano[3,2-c]quinoline Derivatives as New Class of α-glucosidase Inhibitors to Treat Type 2 Diabetes: Synthesis, in vitro Biological Evaluation and Kinetic Study
Medicinal Chemistry Therapeutic Potential of Natural Compounds that Regulate the Activity of Protein Kinase C
Current Medicinal Chemistry Characterization of Probiotic Lactobacillus plantarum MYS14 Isolated from Sannas, a Traditional Fermented Food for its Therapeutic Potential
Current Nutrition & Food Science TC > 0.05 as a Pharmacokinetic Parameter of Paclitaxel for Therapeutic Efficacy and Toxicity in Cancer Patients
Recent Patents on Anti-Cancer Drug Discovery Recent Patents in CNS Drug Discovery: The Management of Inflammation in the Central Nervous System
Recent Patents on CNS Drug Discovery (Discontinued) Enhanced Intracellular Delivery of Curcumin by Chitosan-Lipoic Acid as Reduction-Responsive Nanoparticles
Current Pharmaceutical Biotechnology