Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors
The human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying new hLDH5 inhibitors, a fully automated docking-bas...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-05-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/20/5/8772 |
| _version_ | 1818887037723344896 |
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| author | Carlotta Granchi Alice Capecchi Gianluca Del Frate Adriano Martinelli Marco Macchia Filippo Minutolo Tiziano Tuccinardi |
| author_facet | Carlotta Granchi Alice Capecchi Gianluca Del Frate Adriano Martinelli Marco Macchia Filippo Minutolo Tiziano Tuccinardi |
| author_sort | Carlotta Granchi |
| collection | DOAJ |
| description | The human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying new hLDH5 inhibitors, a fully automated docking-based virtual screening platform was developed by considering different protein conformations and the consensus docking strategy. In order to verify the reliability of the reported platform, a small database of about 10,000 compounds was filtered by using this method, and the top-ranked compounds were tested for their hLDH5 inhibition activity. Enzymatic assays revealed that, among the ten selected compounds, two proved to efficiently inhibit enzyme activity with IC50 values in the micromolar range. These results demonstrate the validity of the methodologies we followed, encouraging the application of larger virtual screening studies and further refinements of the platform. Furthermore, the two active compounds herein described may be considered as interesting leads for the development of new and more efficient LDH inhibitors. |
| first_indexed | 2024-12-19T16:30:52Z |
| format | Article |
| id | doaj.art-744b7d4227654db7acaeec9e82f7e5ab |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-19T16:30:52Z |
| publishDate | 2015-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-744b7d4227654db7acaeec9e82f7e5ab2022-12-21T20:14:12ZengMDPI AGMolecules1420-30492015-05-012058772879010.3390/molecules20058772molecules20058772Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase InhibitorsCarlotta Granchi0Alice Capecchi1Gianluca Del Frate2Adriano Martinelli3Marco Macchia4Filippo Minutolo5Tiziano Tuccinardi6Department of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyThe human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying new hLDH5 inhibitors, a fully automated docking-based virtual screening platform was developed by considering different protein conformations and the consensus docking strategy. In order to verify the reliability of the reported platform, a small database of about 10,000 compounds was filtered by using this method, and the top-ranked compounds were tested for their hLDH5 inhibition activity. Enzymatic assays revealed that, among the ten selected compounds, two proved to efficiently inhibit enzyme activity with IC50 values in the micromolar range. These results demonstrate the validity of the methodologies we followed, encouraging the application of larger virtual screening studies and further refinements of the platform. Furthermore, the two active compounds herein described may be considered as interesting leads for the development of new and more efficient LDH inhibitors.http://www.mdpi.com/1420-3049/20/5/8772LDH inhibitorsvirtual screeningdocking |
| spellingShingle | Carlotta Granchi Alice Capecchi Gianluca Del Frate Adriano Martinelli Marco Macchia Filippo Minutolo Tiziano Tuccinardi Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors Molecules LDH inhibitors virtual screening docking |
| title | Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors |
| title_full | Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors |
| title_fullStr | Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors |
| title_full_unstemmed | Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors |
| title_short | Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors |
| title_sort | development and validation of a docking based virtual screening platform for the identification of new lactate dehydrogenase inhibitors |
| topic | LDH inhibitors virtual screening docking |
| url | http://www.mdpi.com/1420-3049/20/5/8772 |
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