Identification of an aurora kinase inhibitor specific for the aurora B isoform

Hua Xie, Mee Hyun Lee, Feng Zhu, Kanamata Reddy, Cong Peng, Yan Li, Do Young Lim, Dong Joon Kim, Xiang Li, Soouk Kang, Haitao Li, Weiya Ma, Ronald A. Lubet, Jian Ding, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. In the present study, we used a ligand docking method to explore the novel scaffold of potential Aurora B inhibitors. One thousand compounds from our in-house compound library were screened against the Aurora B structure and one compound, (E)-3-((E)-4-(benzo[d][1,3]dioxol-5-yl)-2- oxobut-3-en-1-ylidene)indolin-2-one (designated herein as HOI-07) was selected for further study. HOI-07 potently inhibited in vitro Aurora B kinase activity in a dose-dependent manner, without obvious inhibition of another 49 kinases, including Aurora A. This compound suppressed Aurora B kinase activity in lung cancer cells, evidenced by the inhibition of the phosphorylation of histone H3 on Ser10 in a dose- and time-dependent manner. This inhibition resulted in apoptosis induction, G2-Marrest, polyploidy cells, and attenuation of cancer cell anchorage-independent growth. Moreover, knocking down the expression of Aurora B effectively reduced the sensitivity of cancer cells to HOI-07. Results of an in vivo xenograft mouse study showed that HOI-07 treatment effectively suppressed the growth of A549 xenografts, without affecting the body weight of mice. The expression of phospho-histone H3, phospho- Aurora B, and Ki-67 was also suppressed in the HOI-07 treatment group. Taken together, we identified HOI-07 as a specific Aurora B inhibitor, which deserves further investigation.

Original languageEnglish (US)
Pages (from-to)716-724
Number of pages9
JournalCancer Research
Issue number2
StatePublished - Jan 15 2013


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