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Molecules 2015, 20(5), 8772-8790; doi:10.3390/molecules20058772

Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
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Author to whom correspondence should be addressed.
Academic Editor: Rino Ragno
Received: 3 March 2015 / Revised: 6 May 2015 / Accepted: 11 May 2015 / Published: 15 May 2015
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Abstract

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. View Full-Text
Keywords: LDH inhibitors; virtual screening; docking LDH inhibitors; virtual screening; docking
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Granchi, C.; Capecchi, A.; Del Frate, G.; Martinelli, A.; Macchia, M.; Minutolo, F.; Tuccinardi, T. Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors. Molecules 2015, 20, 8772-8790.

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