Development of the pan-DAC Inhibitor Panobinostat (LBH589): Successes and Challenges

Cancer Lett. 2009 Aug 8;280(2):233-41. doi: 10.1016/j.canlet.2009.02.019. Epub 2009 Apr 2.

Abstract

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 non-histone 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.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Evaluation, Preclinical
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology*
  • Indoles
  • Panobinostat

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Indoles
  • Panobinostat
  • Histone Deacetylases