Belinostat (PXD101) is an inhibitor of hydroxamic acid-type histone deacetylase (HDAC, IC50 of 27 nM in HeLa cell extracts),and with antineoplastic activity.

HDAC:27 nM (Hela cell), HDAC6:82 nM

Belinostat is a novel hydroxamate-type inhibitor of histone deacetylase activity that inhibits histone deacetylase activity in HeLa cell extracts with an IC(50) of 27 nM and induces a concentration-dependent (0.2-5 micro M) increase in acetylation of histone H4 in tumor cell lines.Belinostat is cytotoxic in vitro in a number of tumor cell lines with IC(50)s in the range 0.2-3.4 micro M as determined by a clonogenic assay and induces apoptosis.

Treatment of nude mice bearing human ovarian and colon tumor xenografts with PXD101 (10-40 mg/kg/day i.p.) for 7 days results in a significant, dose-dependent growth delay without obvious signs of toxicity. Growth delay is also observed in xenografts of cisplatin-resistant ovarian tumor cells. A significant increase in acetylation of H4 is detected in blood and tumor tissues 3 hours after treatment. These findings suggest that PXD101 has potential as a novel antitumor agent.