Steroid Sulphatase and Its Inhibitors: Past, Present, and Future
Steroid sulphatase (STS), involved in the hydrolysis of steroid sulphates, plays an important role in the formation of both active oestrogens and androgens. Since these steroids significantly impact the proliferation of both oestrogen- and androgen-dependent cancers, many research groups over the pa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/10/2852 |
| _version_ | 1797534624627294208 |
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| author | Paul A. Foster |
| author_facet | Paul A. Foster |
| author_sort | Paul A. Foster |
| collection | DOAJ |
| description | Steroid sulphatase (STS), involved in the hydrolysis of steroid sulphates, plays an important role in the formation of both active oestrogens and androgens. Since these steroids significantly impact the proliferation of both oestrogen- and androgen-dependent cancers, many research groups over the past 30 years have designed and developed STS inhibitors. One of the main contributors to this field has been Prof. Barry Potter, previously at the University of Bath and now at the University of Oxford. Upon Prof. Potter’s imminent retirement, this review takes a look back at the work on STS inhibitors and their contribution to our understanding of sulphate biology and as potential therapeutic agents in hormone-dependent disease. A number of potent STS inhibitors have now been developed, one of which, Irosustat (STX64, 667Coumate, BN83495), remains the only one to have completed phase I/II clinical trials against numerous indications (breast, prostate, endometrial). These studies have provided new insights into the origins of androgens and oestrogens in women and men. In addition to the therapeutic role of STS inhibition in breast and prostate cancer, there is now good evidence to suggest they may also provide benefits in patients with colorectal and ovarian cancer, and in treating endometriosis. To explore the potential of STS inhibitors further, a number of second- and third-generation inhibitors have been developed, together with single molecules that possess aromatase–STS inhibitory properties. The further development of potent STS inhibitors will allow their potential therapeutic value to be explored in a variety of hormone-dependent cancers and possibly other non-oncological conditions. |
| first_indexed | 2024-03-10T11:32:09Z |
| format | Article |
| id | doaj.art-da5761b5170f497d85f2cbd9e9e73b61 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:32:09Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-da5761b5170f497d85f2cbd9e9e73b612023-11-21T19:11:04ZengMDPI AGMolecules1420-30492021-05-012610285210.3390/molecules26102852Steroid Sulphatase and Its Inhibitors: Past, Present, and FuturePaul A. Foster0Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, UKSteroid sulphatase (STS), involved in the hydrolysis of steroid sulphates, plays an important role in the formation of both active oestrogens and androgens. Since these steroids significantly impact the proliferation of both oestrogen- and androgen-dependent cancers, many research groups over the past 30 years have designed and developed STS inhibitors. One of the main contributors to this field has been Prof. Barry Potter, previously at the University of Bath and now at the University of Oxford. Upon Prof. Potter’s imminent retirement, this review takes a look back at the work on STS inhibitors and their contribution to our understanding of sulphate biology and as potential therapeutic agents in hormone-dependent disease. A number of potent STS inhibitors have now been developed, one of which, Irosustat (STX64, 667Coumate, BN83495), remains the only one to have completed phase I/II clinical trials against numerous indications (breast, prostate, endometrial). These studies have provided new insights into the origins of androgens and oestrogens in women and men. In addition to the therapeutic role of STS inhibition in breast and prostate cancer, there is now good evidence to suggest they may also provide benefits in patients with colorectal and ovarian cancer, and in treating endometriosis. To explore the potential of STS inhibitors further, a number of second- and third-generation inhibitors have been developed, together with single molecules that possess aromatase–STS inhibitory properties. The further development of potent STS inhibitors will allow their potential therapeutic value to be explored in a variety of hormone-dependent cancers and possibly other non-oncological conditions.https://www.mdpi.com/1420-3049/26/10/2852steroid sulphatasecancersulphatase inhibitorSTX64Irosustatdual aromatase–sulphatase inhibitors |
| spellingShingle | Paul A. Foster Steroid Sulphatase and Its Inhibitors: Past, Present, and Future Molecules steroid sulphatase cancer sulphatase inhibitor STX64 Irosustat dual aromatase–sulphatase inhibitors |
| title | Steroid Sulphatase and Its Inhibitors: Past, Present, and Future |
| title_full | Steroid Sulphatase and Its Inhibitors: Past, Present, and Future |
| title_fullStr | Steroid Sulphatase and Its Inhibitors: Past, Present, and Future |
| title_full_unstemmed | Steroid Sulphatase and Its Inhibitors: Past, Present, and Future |
| title_short | Steroid Sulphatase and Its Inhibitors: Past, Present, and Future |
| title_sort | steroid sulphatase and its inhibitors past present and future |
| topic | steroid sulphatase cancer sulphatase inhibitor STX64 Irosustat dual aromatase–sulphatase inhibitors |
| url | https://www.mdpi.com/1420-3049/26/10/2852 |
| work_keys_str_mv | AT paulafoster steroidsulphataseanditsinhibitorspastpresentandfuture |