Tier 3 — preclinical

Discovery of Forvisirvat (DS-7830a/SP-624), a Brain-Penetrant Sirtuin 6 Activator Derived from Griseofulvin with Antidepressant-Like Effects

Yasuyuki Ogawa, Keiji Saito, Katsuyoshi Nakajima, Osamu Iwamoto, Kazumasa Aoki, Mitsuhiro Makino, Shinji Tanaka, Nobuya Kurikawa, Eriko Michishita-Kioi, Seiko Nagata, Yoko Fujita, Masato Sasaki, Akiko Kasahara, Isao Yasumatsu, Makoto Hirasawa, Wataru Saitoh
ACS Medicinal Chemistry Letters 2026 17(9):2038-2044

Bibliography

DOI
10.1021/acsmedchemlett.6c00366
Funding
Daiichi Sankyo Company.
Competing interests
Most authors are employees of Daiichi Sankyo; Masato Sasaki was an employee of Daiichi Sankyo RD Novare when the study was conducted. The authors may own Daiichi Sankyo stock or stock options.

Study snapshot

DesignMedicinal-chemistry lead discovery with photoaffinity labeling, docking, selectivity testing, pharmacokinetics and mouse behavioral pharmacology.
ModelBiochemical SIRT6 assays and preclinical CNS models.
SamplePreclinical experiments; assay-specific sample sizes reported in the paper.
InterventionForvisirvat (DS-7830a/SP-624) and griseofulvin-derived analogues.
DurationExperiment-dependent.
EndpointsSIRT6 activation/selectivity; allosteric binding-site mapping; pharmacokinetics and CNS exposure; antidepressant-like effects in mice

What the study showed, in plain terms

Published in August 2026, this paper explains how forvisirvat was developed from the griseofulvin scaffold into a potent, selective, brain-penetrant SIRT6 activator and maps an allosteric site overlapping the myristoyl pocket.

Key findings

Forvisirvat selectively activated SIRT6 over other sirtuins, showed improved pharmacokinetic/CNS properties, and produced antidepressant-like effects in mouse models.

What this study can and cannot tell us

This is company-funded preclinical drug-discovery work. Human efficacy and long-term safety must be judged from clinical trials.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability