Title: The Discovery of Daclatasvir: from Phenotype Screen Hit to First-in-Class HCV NS5A
Inhibitor
Abstract: High throughput screening of the BMS compound collection afforded a mechanistically
unique thiazolidinone hit exhibiting a sub-micromolar inhibitory potency towards an HCV replicon.
Raising and mapping of resistance mutation indicated that the NS5A Protein, a key protein with a multifunctional role in the virus’ replication cycle, was the most likely target. Highlights of the medicinal
chemistry campaign that optimized this hit to the highly potent first-in-class HCV NS5A inhibitor
daclatavir along with key clinical results will be discussed.
Relevant references (and references therein)
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