Three-Dimensional Analysis of the Interactions between hLDH5 and Its Inhibitors.

Inhibitors of human lactate dehydrogenase ( h LDH5)-the enzyme responsible for the conversion of pyruvate to lactate coupled with oxidation of NADH to NAD⁺-are promising therapeutic agents against cancer because this enzyme is generally found to be overexpressed in most invasive cancer cells and is linked to their vitality especially under hypoxic conditions. Consequently, significant efforts have been made for the identification of small-molecule h LDH5 inhibitors displaying high inhibitory potencies. X-ray structure of h LDH5 complexes as well as molecular modeling studies contribute to identify and explain the main binding modes of h LDH5 inhibitors reported in literature. The purpose of this review is to analyze the main three-dimensional interactions between some of the most potent inhibitors and h LDH5, in order to provide useful suggestions for the design of new derivatives.