Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling

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The human lactate dehydrogenase isoform A plays an important role in the anaerobic metabolism of tumour cells and therefore constitutes an attractive target in the oncology field. Full-atom models of lactate dehydrogenase A (in complex with NADH and in the apo form) have been generated to enable structure-based design of novel inhibitors competing with pyruvate and NADH. The structural criteria for the selection of potential inhibitors were established, and virtual screening of a library of low-molecular-weight compounds was performed. A potential inhibitor, STK381370, was identified whose docking pose was stabilized through additional interactions with the loop 96-111 providing for the transition from the open to the closed conformation.

About the authors

D. K. Nilov

Lomonosov Moscow State University

Author for correspondence.
Russian Federation

E. A. Prokhorova

Lomonosov Moscow State University

Russian Federation

V. K. Švedas1

Lomonosov Moscow State University

Russian Federation


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Copyright (c) 2015 Nilov D.K., Prokhorova E.A., Švedas1 V.K.

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