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High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Discovery of macrocyclic HDACs 1, 2, and 3 selective inhibitors for HIV latency reactivation
Wensheng Yu1, James Fells2, Dane Clausen1
1Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Abstract:
A series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors were identified with good enzymatic activity and high selectivity over HDACs 6 and 8. These macrocyclic HDAC inhibitors used an ethyl ketone as the zinc-binding group. Compounds 25 and 26 stood out as leads due to their low double-digit nM EC50s in the 2C4 cell-based HIV latency reactivation assay. The PK profiles of these macrocyclic HDAC inhibitors still needed improvement.
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