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Updated: May 24, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
Design and synthesis of novel lactate dehydrogenase A inhibitors by fragment-based lead generation
Richard A Ward1, Claire Brassington, Alexander L Breeze
1Oncology and Discovery Sciences iMEDs, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. richard.a.ward@astrazeneca.com
Abstract:
Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.
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