Targeting LSD1 for acute myeloid leukemia (AML) treatment

Shujing Zhang; Menghan Liu; Yongfang Yao; Bin Yu; Hongmin Liu

doi:10.1016/j.phrs.2020.105335

Targeting LSD1 for acute myeloid leukemia (AML) treatment

Pharmacol Res. 2021 Feb:164:105335. doi: 10.1016/j.phrs.2020.105335. Epub 2020 Dec 4.

Authors

Shujing Zhang¹, Menghan Liu¹, Yongfang Yao², Bin Yu³, Hongmin Liu⁴

Affiliations

¹ School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China.
² School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450052, PR China. Electronic address: yongfangyao@zzu.edu.cn.
³ School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450052, PR China. Electronic address: zzuyubin@hotmail.com.
⁴ School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450052, PR China. Electronic address: liuhm@zzu.edu.cn.

PMID: 33285227
DOI: 10.1016/j.phrs.2020.105335

Abstract

Targeted therapy for acute myeloid leukemia (AML) is an effective strategy, but currently there are very limited therapeutic targets for AML treatment. Histone lysine specific demethylase 1 (LSD1) is highly expressed in many cancers, impedes the differentiation of cancer cells, promotes the proliferation, metastasis and invasion of cancer cells, and is associated with poor prognosis. Targeting LSD1 has been recognized as a promising strategy for AML treatment in recent years. Based on these features, in the review, we discussed the main epigenetic drugs targeting LSD1 for AML therapy. Thus, this review focuses on the progress of LSD1 inhibitors in AML treatment, particularly those such as tranylcypromine (TCP), ORY-1001, GSK2879552, and IMG-7289 in clinical trials. These inhibitors provide novel scaffolds for designing new LSD1 inhibitors. Besides, combined therapies of LSD1 inhibitors with other drugs for AML treatment are also highlighted.

Keywords: AML treatment; Combination therapy; Histone demethylase; LSD1 inhibitors; Tranylcypromine derivatives.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Histone Demethylases / antagonists & inhibitors*
Histone Demethylases / metabolism
Humans
Leukemia, Myeloid, Acute / drug therapy*
Leukemia, Myeloid, Acute / metabolism
Molecular Targeted Therapy

Substances

Antineoplastic Agents
Histone Demethylases
KDM1A protein, human