Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics.
Epigenetic processes are the critical events in carcinogenesis. Histone modification plays a crucial role in gene expression regulation, where histone deacetylases (HDACs) are key players in epigenetic processes. Inhibiting HDACs has shown promise in modern cancer therapy. However, the non-selective...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316343 |
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| author | Mohammed Alrouji Sabina Yasmin Mohammed S Alshammari Fahad A Alhumaydhi Sharaf E Sharaf Moyad Shahwan Anas Shamsi |
| author_facet | Mohammed Alrouji Sabina Yasmin Mohammed S Alshammari Fahad A Alhumaydhi Sharaf E Sharaf Moyad Shahwan Anas Shamsi |
| author_sort | Mohammed Alrouji |
| collection | DOAJ |
| description | Epigenetic processes are the critical events in carcinogenesis. Histone modification plays a crucial role in gene expression regulation, where histone deacetylases (HDACs) are key players in epigenetic processes. Inhibiting HDACs has shown promise in modern cancer therapy. However, the non-selective nature and drug resistance of most HDAC inhibitors (HDACIs) limits their clinical use. This limitation prompts a search for isoform-selective and more effective inhibitors. Histone deacetylase 1 (HDAC1) is a member of the class I HDAC family and has emerged as a promising target in various diseases, including cancer and neurodegeneration. Drug repurposing has gained significant interest in identifying treatments for new targets, which involves finding new uses for existing drugs beyond their original medical indications. Here, we employed virtual screening of repurposed drugs from the DrugBank database to identify potential HDAC1 inhibitors. We conducted a series of analyses, including molecular docking, drug profiling, PASS evaluation, and interaction analysis. Molecular dynamics (MD) simulations and MM-PBSA analysis were also performed for 300 ns. Through these analyses, we pinpointed Alectinib, which exhibits a promising drug profile in PASS analysis and higher affinity and efficiency for HDAC1 than the reference inhibitor. MD simulations revealed that Alectinib stabilizes HDAC1 with minimal structural perturbations. The findings suggest that Alectinib holds promise as a therapeutic lead for HDAC1-associated carcinogenesis after required validation. |
| format | Article |
| id | doaj-art-38724163ca1a4ba0ba4b853f09fcd9ed |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-38724163ca1a4ba0ba4b853f09fcd9ed2025-01-08T05:31:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031634310.1371/journal.pone.0316343Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics.Mohammed AlroujiSabina YasminMohammed S AlshammariFahad A AlhumaydhiSharaf E SharafMoyad ShahwanAnas ShamsiEpigenetic processes are the critical events in carcinogenesis. Histone modification plays a crucial role in gene expression regulation, where histone deacetylases (HDACs) are key players in epigenetic processes. Inhibiting HDACs has shown promise in modern cancer therapy. However, the non-selective nature and drug resistance of most HDAC inhibitors (HDACIs) limits their clinical use. This limitation prompts a search for isoform-selective and more effective inhibitors. Histone deacetylase 1 (HDAC1) is a member of the class I HDAC family and has emerged as a promising target in various diseases, including cancer and neurodegeneration. Drug repurposing has gained significant interest in identifying treatments for new targets, which involves finding new uses for existing drugs beyond their original medical indications. Here, we employed virtual screening of repurposed drugs from the DrugBank database to identify potential HDAC1 inhibitors. We conducted a series of analyses, including molecular docking, drug profiling, PASS evaluation, and interaction analysis. Molecular dynamics (MD) simulations and MM-PBSA analysis were also performed for 300 ns. Through these analyses, we pinpointed Alectinib, which exhibits a promising drug profile in PASS analysis and higher affinity and efficiency for HDAC1 than the reference inhibitor. MD simulations revealed that Alectinib stabilizes HDAC1 with minimal structural perturbations. The findings suggest that Alectinib holds promise as a therapeutic lead for HDAC1-associated carcinogenesis after required validation.https://doi.org/10.1371/journal.pone.0316343 |
| spellingShingle | Mohammed Alrouji Sabina Yasmin Mohammed S Alshammari Fahad A Alhumaydhi Sharaf E Sharaf Moyad Shahwan Anas Shamsi Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics. PLoS ONE |
| title | Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics. |
| title_full | Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics. |
| title_fullStr | Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics. |
| title_full_unstemmed | Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics. |
| title_short | Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics. |
| title_sort | virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of histone deacetylase 1 implication in cancer therapeutics |
| url | https://doi.org/10.1371/journal.pone.0316343 |
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