ArticleACS medicinal chemistry letters2026
Discovery of Forvisirvat (DS-7830a/SP-624), a Brain-Penetrant Sirtuin 6 Activator Derived from Griseofulvin with Antidepressant-Like Effects.
Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
We report the discovery of forvisirvat (DS-7830a/SP-624), a potent and selective brain-penetrant activator of sirtuin 6 (SIRT6) derived from natural product griseofulvin. Photoaffinity labeling combined with molecular docking identified an allosteric binding site that overlaps with the substrate myristoyl pocket. SAR studies focused on C-6 modification yielded forvisirvat with markedly improved pharmacokinetic properties and CNS exposure. Forvisirvat selectively activated SIRT6 over other sirtuin isoforms and exhibited robust antidepressant-like effects in mouse models, supporting the therapeutic potential of SIRT6 activation in depression.
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