Preclinical antileukemia activity of JNJ-26481585, a potent second-generation histone deacetylase inhibitor

Histone deacetylase (HDAC) inhibitors have been shown to induce cell cycle arrest, terminal differentiation, and apoptosis in a broad spectrum of human tumors and animal xenograft models. JNJ-26481585 is a hydroxamic acid derivative, second-generation pan-HDAC inhibitor that has demonstrated high potency in preclinical studies. In the current study, we demonstrated that JNJ-26481585 has antileukemia and molecular activity in leukemia cell lines and primary human leukemia cells. We also observed a synergistic effect between treatment with decitabine and JNJ-26481585. In conclusion, JNJ-26481585 is a potent second-generation pan-HDAC inhibitor with activity in human leukemia, and it is currently in clinical development. (C) 2009 Elsevier Ltd. All rights reserved.