Potent inhibitors of equine steroid isomerase EcaGST A3-3.
Equine glutathione transferase A3-3 (EcaGST A3-3) belongs to the superfamily of detoxication enzymes found in all higher organisms. However, it is also the most efficient steroid double-bond isomerase known in mammals. Equus ferus caballus shares the steroidogenic pathway with Homo sapiens, which ma...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0214160 |
| _version_ | 1830358307602169856 |
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| author | Helena Lindström Aslam M A Mazari Yaman Musdal Bengt Mannervik |
| author_facet | Helena Lindström Aslam M A Mazari Yaman Musdal Bengt Mannervik |
| author_sort | Helena Lindström |
| collection | DOAJ |
| description | Equine glutathione transferase A3-3 (EcaGST A3-3) belongs to the superfamily of detoxication enzymes found in all higher organisms. However, it is also the most efficient steroid double-bond isomerase known in mammals. Equus ferus caballus shares the steroidogenic pathway with Homo sapiens, which makes the horse a suitable animal model for investigations of human steroidogenesis. Inhibition of the enzyme has potential for treatment of steroid-hormone-dependent disorders. Screening of a library of FDA-approved drugs identified 16 out of 1040 compounds, which at 10 μM concentration afforded at least 50% inhibition of EcaGST A3-3. The most potent inhibitors, anthralin, sennoside A, tannic acid, and ethacrynic acid, were characterized by IC50 values in the submicromolar range when assayed with the natural substrate Δ5-androstene-3,17-dione. |
| first_indexed | 2024-12-20T02:39:56Z |
| format | Article |
| id | doaj.art-f738c4f55e51402ea11f67f1dba7e3b1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:39:56Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f738c4f55e51402ea11f67f1dba7e3b12022-12-21T19:56:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021416010.1371/journal.pone.0214160Potent inhibitors of equine steroid isomerase EcaGST A3-3.Helena LindströmAslam M A MazariYaman MusdalBengt MannervikEquine glutathione transferase A3-3 (EcaGST A3-3) belongs to the superfamily of detoxication enzymes found in all higher organisms. However, it is also the most efficient steroid double-bond isomerase known in mammals. Equus ferus caballus shares the steroidogenic pathway with Homo sapiens, which makes the horse a suitable animal model for investigations of human steroidogenesis. Inhibition of the enzyme has potential for treatment of steroid-hormone-dependent disorders. Screening of a library of FDA-approved drugs identified 16 out of 1040 compounds, which at 10 μM concentration afforded at least 50% inhibition of EcaGST A3-3. The most potent inhibitors, anthralin, sennoside A, tannic acid, and ethacrynic acid, were characterized by IC50 values in the submicromolar range when assayed with the natural substrate Δ5-androstene-3,17-dione.https://doi.org/10.1371/journal.pone.0214160 |
| spellingShingle | Helena Lindström Aslam M A Mazari Yaman Musdal Bengt Mannervik Potent inhibitors of equine steroid isomerase EcaGST A3-3. PLoS ONE |
| title | Potent inhibitors of equine steroid isomerase EcaGST A3-3. |
| title_full | Potent inhibitors of equine steroid isomerase EcaGST A3-3. |
| title_fullStr | Potent inhibitors of equine steroid isomerase EcaGST A3-3. |
| title_full_unstemmed | Potent inhibitors of equine steroid isomerase EcaGST A3-3. |
| title_short | Potent inhibitors of equine steroid isomerase EcaGST A3-3. |
| title_sort | potent inhibitors of equine steroid isomerase ecagst a3 3 |
| url | https://doi.org/10.1371/journal.pone.0214160 |
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