Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges

The histone deacetylase (HDAC) inhibitors are emerging as a highly useful class of anticancer agents that inhibit the enzyme HDAC involved in the deacetylation of histone and nonhistone cellular proteins. The HDAC inhibitor, panobinostat (LBH589, Novartis Pharmaceuticals), achieves potent inhibition of all HDAC enzymes implicated in cancer and has demonstrated potent anti-tumor activity in preclinical models and promising clinical efficacy in cancer patients. In this review we discuss the successes and challenges surrounding the development of panobinostat, focusing on its proposed mechanism of action, preclinical anti-tumor activity, and early clinical efficacy in hematologic and solid tumors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.