Forvisirvat (SP-624) is a selective, orally active sirtuin 6 (SIRT6) activator with EC150 of 1.2 uM.
SP-624 activates SIRT6 deacetylation of histone peptides and deacetylation of H3K9 and H3K18 in intact nucleosomes.
SP-624 is active in multiple animal models used to predict efficacy for depression in humans, including tests in adrenocorticotropic hormone‐treated mice and olfactory bulbectomized rats.
SP-624 also prevents cognitive deficits induced by scopolamine (anticholinergic) or phencyclidine (N-methyl-D-aspartate antagonist) in the novel object recognition test and suppressed excessive cytokine release in animal models.
