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

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.

SUBMITTER: Nilov DK

PROVIDER: S-EPMC4463413 | biostudies-literature | 2015 Apr-Jun

REPOSITORIES: biostudies-literature

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

Nilov D K DK Prokhorova E A EA Švedas V K VK

Acta naturae 20150401 2

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- ...[more]

PMID: 26085945

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