Citarinostat (ACY241) is a second generation potent, orally active and high-selective HDAC6 inhibitor with an IC₅₀ of 2.6 nM (IC₅₀s of 35 nM, 45 nM, 46 nM and 137 nM for HDAC1, HDAC2, HDAC3 and HDAC8, respectively). Citarinostat has anticancer effects^[1]. In Vitro: Citarinostat (ACY241; 0-3 μM; 24 hours; A2780 cells) treatment with 300 nM results in increased hyperacetylation of α-tubulin, consistent with inhibition of the tubulin deacetylase HDAC6. In contrast, hyperacetylation of histone H3, a target of Class I HDACs, is only observed at doses above 1 μM. Low exposures of Citarinostat result in selective inhibition of HDAC6, while higher exposures lead to inhibition of Class I HDAC isozymes^[1].
The single agent viability IC₅₀ of Citarinostat (ACY241) ranged from 4.6-6.1 μM in A2780 and TOV-21G ovarian cancer and MDA-MD-231 breast cancer cells. Consistent with the viability assay, single agent Citarinostat modestly reduces proliferation at doses up to 3 μM without inducing apoptosis, while 10 μM of Citarinostat causes significant induction of apoptosis and completely suppresses proliferation^[1]. In Vivo: Citarinostat (ACY241; 50 mg/kg; intraperitoneal injection; once daily for five days, followed by two days off; for 3 weeks; female athymic nude mice) significantly suppresses tumor growth in combination with NSC 125973^[1].