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Updated: Jul 6, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Design and campaign synthesis of piperidine- and thiazole-based histone deacetylase inhibitors
David M Andrews1, Elaine S E Stokes, Greg R Carr
1Cancer and Infection Research, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK. david.andrews@astrazeneca.com
Abstract:
A lead benzamide, 3, was identified as a potent and low molecular weight histone deacetylase (HDAC) inhibitor. Optimization led to 16d, demonstrating an excellent balance of efficacy and non-efficacy properties, along with very desirable in vivo DMPK. The final compounds presented are >1000-fold more potent than the initial screen hit, an improvement in potency which was achieved with a concomitant significant improvement in all the main non-efficacy properties.
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