Research Papers:

Identification of JL1037 as a novel, specific, reversible lysine-specific demethylase 1 inhibitor that induce apoptosis and autophagy of AML cells

Shuang Liu, Wenting Lu, Shouyun Li, Saisai Li, Jia Liu, Yuanyuan Xing, Shuzu Zhang, Joe Zhongxiang Zhou, Haiyan Xing, Yingxi Xu, Qing Rao, Chengjun Deng, Min Wang and Jianxiang Wang _

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Oncotarget. 2017; 8:31901-31914. https://doi.org/10.18632/oncotarget.16650

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Shuang Liu1, Wenting Lu1, Shouyun Li1, Saisai Li1, Jia Liu1, Yuanyuan Xing2, Shuzu Zhang2, Joe Zhongxiang Zhou2, Haiyan Xing1, Yingxi Xu1, Qing Rao1, Chengjun Deng2, Min Wang1, Jianxiang Wang1

1State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China

2Fujian Jinler Pharmaceuticals, Jiangle County, Fujian 353300, China

Correspondence to:

Chengjun Deng, email: [email protected]

Min Wang, email: [email protected]

Jianxiang Wang, email: [email protected]

Keywords: LSD1 inhibitor, leukemia, proliferation inhibition, apoptosis, autophagy

Received: December 09, 2016     Accepted: March 15, 2017     Published: March 29, 2017


Lysine-specific demethylase 1 (LSD1) has been recognized as a potential therapeutic target for acute myeloid leukemia (AML). Herein, we identified a novel LSD1 inhibitor, JL1037, via Computer Aided Drug Design technology. JL1037 is a potent, selective and reversible LSD1 inhibitor with IC50s of 0.1 μM and >1.5 μM for LSD1 and monoamine oxidases A/B (MAO-A/B), respectively. Treatment of THP-1 and Kasumi-1 cell lines with JL1037 resulted in dose dependent accumulation of H3K4me1 and H3K4me2, the major substrates of LSD1, as well as inhibition of cell proliferation, blockade of cell cycle and induction of apoptosis. Further investigations demonstrated that JL1037 could upregulate cell cycle-related proteins P21, P57, pro-apoptotic protein Bax and downregulate anti-apoptosis proteins Bcl-2 and Bcl-XL. JL1037 appeared to activate autophage response in AML cell lines as well as primary cells from AML patients by increasing LC3-II expression and the formation of autophagosomes and autolysosomes in cytoplasm. Co-treatment with autophagy inhibitor chloroquine (CQ) enhanced JL1037-induced cell apoptosis. Moreover, daily intravenous administration of JL1037 tended to reduce tumor burden and prolong the survival of t(8;21) leukemia mice. In conclusion, JL1037 exhibited potent anti-leukemia effect and could be a potential therapeutic agent for AML treatment.

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