| Autor: |
Ester Colarusso, Erica Gazzillo, Eleonora Boccia, Stefania Terracciano, Ines Bruno, Giuseppe Bifulco, Maria Giovanna Chini, Gianluigi Lauro |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Molecules, Vol 29, Iss 17, p 4025 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1420-3049 |
| DOI: |
10.3390/molecules29174025 |
| Popis: |
A 3D structure-based pharmacophore model built for bromodomain-containing protein 4 (BRD4) is reported here, specifically developed for investigating and identifying the key structural features of the (+)-JQ1 known inhibitor within the BRD4 binding site. Using this pharmacophore model, 273 synthesized and purchased compounds previously considered for other targets but yielding poor results were screened in a drug repositioning campaign. Subsequently, only six compounds showed potential as BRD4 binders and were subjected to further biophysical and biochemical assays. Compounds 2, 5, and 6 showed high affinity for BRD4, with IC50 values of 0.60 ± 0.25 µM, 3.46 ± 1.22 µM, and 4.66 ± 0.52 µM, respectively. Additionally, these compounds were tested against two other bromodomains, BRD3 and BRD9, and two of them showed high selectivity for BRD4. The reported 3D structure-based pharmacophore model proves to be a straightforward and useful tool for selecting novel BRD4 ligands. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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