Histone lysine-specific demethylase 1 (LSD1/KDM1A) has become an important and promising anticancer target since it was first identified in 2004 and specially demethylates lysine residues of histone H3K4me1/2 and H3K9me1/2. LSD1 is ubiquitously overexpressed in diverse cancers, and abrogation of LSD1 results in inhibition of proliferation, invasion, and migration in cancer cells. Over the past decade, a number of biologically active small-molecule LSD1 inhibitors have been developed. To date, six trans-2-phenylcyclopropylamine (TCP)-based LSD1 inhibitors (including TCP, ORY-1001, GSK-2879552, INCB059872, IMG-7289, and ORY-2001) that covalently bind to the flavin adenine dinucleotide (FAD) within the LSD1 catalytic cavity have already entered into clinical trials. Here, we provide an overview about the structures, activities, and structure–activity relationship (SAR) of TCP-based LSD1 inhibitors that mainly covers the literature from 2008 to date. The opportunities, challenges, and future research directions in this emerging and promising field are also discussed.

中文翻译：

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基于Tranylcypromine的LSD1抑制剂：概述和展望。

自组蛋白赖氨酸特异性脱甲基酶1（LSD1 / KDM1A）于2004年首次被发现以来，它已成为重要且有希望的抗癌靶标，并特别使组蛋白H3K4me1 / 2和H3K9me1 / 2的赖氨酸残基脱甲基。LSD1在各种癌症中普遍存在过表达，而LSD1的废除会抑制癌细胞的增殖，侵袭和迁移。在过去的十年中，已经开发了许多具有生物活性的小分子LSD1抑制剂。迄今为止，六个反式基于-2-苯基环丙胺（TCP）的LSD1抑制剂（包括TCP，ORY-1001，GSK-2879552，INCB059872，IMG-7289和ORY-2001）与LSD1催化腔内的黄素腺嘌呤二核苷酸（FAD）共价结合已经进入临床试验。在这里，我们提供了有关基于TCP的LSD1抑制剂的结构，活性和构效关系（SAR）的概述，主要涵盖了2008年至今的文献。还讨论了这个新兴和有前途的领域中的机遇，挑战和未来的研究方向。