Figure 1.

A. Structure of Cpd-60 and CI-994. B. In vitro HDAC inhibition IC₅₀ values following 60 or 180^a min incubation of enzyme with substrate and inhibitor indicate selectivity of slow-binding test compounds for a subset of class I HDAC enzymes with no appreciable inhibition of HDAC8 or class II enzymes. C. In vivo pharmacokinetics in mouse brain following i.p. injection of Cpd-60 (45 mg/kg) or CI-994 (10mg/kg) indicate HDAC inhibitors (HDACi) reach peak concentrations within one hour and remain present in brain at >100 nM for at least eight hours. The brain concentration of each inhibitor exceeds the IC₅₀ for targeted HDACs.