Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2
Prolyl hydroxylase (PHD) enzymes play a critical role in the cellular responses to hypoxia through their regulation of the hypoxia inducible factor α (HIF-α) transcription factors. PHD inhibitors show promise for the treatment of diseases including anaemia, cardiovascular disease and stroke. In this...
| Main Authors: | , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
Elsevier
2021
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| _version_ | 1826313007211216896 |
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| author | Richardson, NL O'Malley, LJ Weissberger, D Tumber, A Schofield, CJ Griffith, R Jones, NM Hunter, L |
| author_facet | Richardson, NL O'Malley, LJ Weissberger, D Tumber, A Schofield, CJ Griffith, R Jones, NM Hunter, L |
| author_sort | Richardson, NL |
| collection | OXFORD |
| description | Prolyl hydroxylase (PHD) enzymes play a critical role in the cellular responses to hypoxia through their regulation of the hypoxia inducible factor α (HIF-α) transcription factors. PHD inhibitors show promise for the treatment of diseases including anaemia, cardiovascular disease and stroke. In this work, a pharmacophore-based virtual high throughput screen was used to identify novel potential inhibitors of human PHD2. Two moderately potent new inhibitors were discovered, with IC<sub>50</sub> values of 4 μM and 23 μM respectively. Cell-based studies demonstrate that these compounds exhibit protective activity in neuroblastoma cells, suggesting that they have the potential to be developed into clinically useful neuroprotective agents. |
| first_indexed | 2024-03-07T04:34:07Z |
| format | Journal article |
| id | oxford-uuid:cf5a08fb-18a6-4c68-85a1-0a8c2d576c42 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:04:09Z |
| publishDate | 2021 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:cf5a08fb-18a6-4c68-85a1-0a8c2d576c422024-05-14T10:25:41ZDiscovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cf5a08fb-18a6-4c68-85a1-0a8c2d576c42EnglishSymplectic ElementsElsevier2021Richardson, NLO'Malley, LJWeissberger, DTumber, ASchofield, CJGriffith, RJones, NMHunter, LProlyl hydroxylase (PHD) enzymes play a critical role in the cellular responses to hypoxia through their regulation of the hypoxia inducible factor α (HIF-α) transcription factors. PHD inhibitors show promise for the treatment of diseases including anaemia, cardiovascular disease and stroke. In this work, a pharmacophore-based virtual high throughput screen was used to identify novel potential inhibitors of human PHD2. Two moderately potent new inhibitors were discovered, with IC<sub>50</sub> values of 4 μM and 23 μM respectively. Cell-based studies demonstrate that these compounds exhibit protective activity in neuroblastoma cells, suggesting that they have the potential to be developed into clinically useful neuroprotective agents. |
| spellingShingle | Richardson, NL O'Malley, LJ Weissberger, D Tumber, A Schofield, CJ Griffith, R Jones, NM Hunter, L Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2 |
| title | Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2 |
| title_full | Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2 |
| title_fullStr | Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2 |
| title_full_unstemmed | Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2 |
| title_short | Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2 |
| title_sort | discovery of neuroprotective agents that inhibit human prolyl hydroxylase phd2 |
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