TCPs：用于鉴定癌症治疗有效 LSD1 抑制剂的特殊支架
TCPs: privileged scaffolds for identifying potent LSD1 inhibitors for cancer therapy.
作者信息
Zheng Yi-Chao, Yu Bin, Chen Zhe-Sheng, Liu Ying, Liu Hong-Min
机构信息
Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China; Co-innovation Center of Henan Province for New drug R&D & Preclinical Safety; Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China.
College of Pharmacy & Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York, NY 11439, USA.
出版信息
Epigenomics. 2016 May;8(5):651-66. doi: 10.2217/epi-2015-0002. Epub 2016 Apr 22.
Since the first lysine-specific demethylase (KDM), lysine-specific demethylase 1 (LSD1), was characterized in 2004, several families of KDMs have been identified. LSD1 can specifically demethylate H3K4me1/2, H3K9me1/2 as well as some nonhistone substrates. It has been demonstrated to be an oncogene as well as a drug target. Hence, tens of small-molecule LSD1 inhibitors have been designed, synthesized and applied for cancer treatment. However, the two LSD1 inhibitors that have been advanced into early phase clinical trials are trans-2-phenylcyclopropylamine (TCP) derivatives, which indicate that TCP is a druggable scaffold for LSD1 inhibitor. Here, we review the design, synthesis and properties of reported TCP-based LSD1 inhibitors as well as their biological roles.
自2004年首个赖氨酸特异性去甲基化酶（KDM）——赖氨酸特异性去甲基化酶1（LSD1）被鉴定以来，已鉴定出多个KDM家族。LSD1可以特异性地使H3K4me1/2、H3K9me1/2以及一些非组蛋白底物去甲基化。它已被证明是一种癌基因以及药物靶点。因此，已经设计、合成了数十种小分子LSD1抑制剂并将其应用于癌症治疗。然而，已进入早期临床试验的两种LSD1抑制剂是反式-2-苯基环丙胺（TCP）衍生物，这表明TCP是LSD1抑制剂的可成药骨架。在此，我们综述了已报道的基于TCP的LSD1抑制剂的设计、合成和性质及其生物学作用。
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