(S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxaMide

ChEBI: CHIC-35 is an organic heterotricyclic compound resulting from the formal fusion of the 2-3 bond of 5-chloroindole with the 2-3 bond of cycloheptanecarboxamide (the S enantiomer). It is a potent, cell-permeable, metabolically stable and selective inhibitor of the deacetylase SIRT1. It has a role as an EC 3.5.1.98 (histone deacetylase) inhibitor. It is an aromatic compound, an organic heterotricyclic compound, an organochlorine compound and a primary carboxamide.

A cell-permeable entiomerically pure compound that is structurally similar to and exhibits similar potency (IC₅₀ = 63 nM) and selectivity as SIRT1 Inhibitor III (Cat. No. 566322). Shown to be orally bioavailable with a serum half-life of 94 minutes in mice in vivo.

CHIC-35 is cell-permeable, metabolically stable, and very potent inhibitor of SIRT1; IC50 of S-isomer is 60 nM; IC50 of mixed isomers is 124 nM. There is no inhibition of SIRT3 or HDAC. The IC50 for SIRT2 is 2.77 μM. Sirtuins are protein deacetylases, which represent a new class of histone deacetylases (HDAC) involved in gene silencing. SIRT modulators are potential therapeutics for cancer, diabetes, muscle differentiation, heart failure, neurodegeneration, and aging.