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

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Abstract

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.
Email: nilov@belozersky.msu.ru
Россия

E. A. Prokhorova

Lomonosov Moscow State University

Email: nilov@belozersky.msu.ru
Россия

V. K. Švedas1

Lomonosov Moscow State University

Email: nilov@belozersky.msu.ru
Россия

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

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