School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, PR China.
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.
Pharmacol Res. 2021 Feb;164:105335. doi: 10.1016/j.phrs.2020.105335. Epub 2020 Dec 4.
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.
靶向治疗急性髓系白血病（AML）是一种有效的策略，但目前 AML 的治疗靶点非常有限。组蛋白赖氨酸特异性去甲基化酶 1（LSD1）在许多癌症中高度表达，阻碍癌细胞的分化，促进癌细胞的增殖、转移和侵袭，并与不良预后相关。近年来，靶向 LSD1 已被认为是 AML 治疗的一种有前途的策略。基于这些特点，在综述中，我们讨论了针对 AML 治疗的 LSD1 的主要表观遗传药物。因此，本综述重点介绍了 LSD1 抑制剂在 AML 治疗中的进展，特别是临床试验中的曲奈普汀（TCP）、ORY-1001、GSK2879552 和 IMG-7289 等抑制剂。这些抑制剂为设计新型 LSD1 抑制剂提供了新的骨架。此外，还强调了 LSD1 抑制剂与其他药物联合治疗 AML 的方法。
