A Virtual Screening Study for Lactate Dehydrogenase 5 Inhibitors by Using a Pharmacophore-based Approach.

Abstract

Inhibitors of human lactate dehydrogenase 5 (hLDH5) are promising therapeutic agents against cancer. This enzyme is generally found to be overexpressed in most invasive cancer cells and is linked to their vitality especially under hypoxic conditions. In this study, with the aim of identifying new hLDH5 inhibitors, a receptor-based pharmacophore modeling approach has been tested and, in order to verify the reliability of the reported approach, the Gold and Platinum database from Asinex were filtered. The top-ranked compounds were experimentally tested for their hLDH5 inhibition activity and enzymatic assays revealed that, among the ten selected compounds, two proved to inhibit the enzyme activity with Ki values in the micromolar range (Ki =33.1-76.7 μM).