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Updated: Apr 20, 2026

Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue
Published on: June 21, 2018
Identification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase
Benjamin P Fauber1, Peter S Dragovich1, Jinhua Chen2
1Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Abstract:
A series of 3,6-disubstituted dihydropyrones were identified as inhibitors of human lactate dehydrogenase (LDH)-A. Structure activity relationships were explored and a series of 6,6-spiro analogs led to improvements in LDHA potency (IC50 <350 nM). An X-ray crystal structure of an improved compound bound to human LDHA was obtained and it illustrated additional opportunities to enhance the potency of these compounds, resulting in the identification of 51 (IC50=30 nM).
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