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.
Tong
Wei-Gang
WG
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States.
Wei
Yue
Y
Stevenson
William
W
Kuang
Shao-Qing
SQ
Fang
Zhihong
Z
Zhang
Ming
M
Arts
Janine
J
Garcia-Manero
Guillermo
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077209:Decitabine; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C541788:quisinostat; D000077209:Decitabine; D001374:Azacitidine