Annual review of lysine-specific demethylase 1 (LSD1/KDM1A) inhibitors in 2021
Annual review of lysine-specific demethylase 1 (LSD1/KDM1A) inhibitors in 2021
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2021年赖氨酸特异性去甲基酶1（LSD1/KDM1A）抑制剂年度综述
DOI：
10.1016/j.ejmech.2021.114042
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发表时间：
2022
影响因子：
6.7
通讯作者：
Bin Yu
中科院分区：
文献类型：
--
作者：
Yihui Song;Huiqing Zhang;Xiaoke Yang;Yuting Shi;Bin Yu
赖氨酸特异性脱甲基酶1（LSD 1/KDM 1A）已成为一种有前途的疾病治疗的表观遗传靶点。几种LSD 1抑制剂已进入临床试验阶段。继我们于2020年对LSD 1抑制剂进行的最后一次年度审查（Eur. J. Med. Chem. 2021，214，113254），在这篇综述中，我们旨在更新2021年期间报道的LSD 1抑制剂，包括天然产物，合成化合物和环肽。设计策略，结构-活性关系，结合模型分析和行动模式突出。特别是，两种FDA批准的抗高血压药物雷洛昔芬和非诺多泮被重新用作可逆的LSD 1抑制剂。确定了治疗神经发育障碍的临床候选药物TAK-418和LSD 1的PET显像剂[18 F] 30。此外，靶向LSD 1和HDAC 6或微管蛋白的双重抑制剂显示出比单一药物增强的抗癌作用。这些化合物进一步丰富了LSD 1抑制剂的结构类型。
Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising epigenetic target for disease treatment. Several LSD1 inhibitors have advanced into clinical trials. Following our last annual review on LSD1 inhibitors in 2020 (Eur. J. Med. Chem. 2021, 214, 113254), in this review we aim to update LSD1 inhibitors including natural products, synthetic compounds and cyclic peptides reported during 2021. Design strategies, structure-activity relationships, binding model analysis and modes of action are highlighted. In particular, two FDA-approved antihypertensive drugs raloxifene and fenoldopam were repurposed as reversible LSD1 inhibitors. The clinical candidateTAK-418for treating neurodevelopmental disorders and PET imaging agent [18F]30for LSD1 were identified. Moreover, dual inhibitors targeting both LSD1 and HDAC6 or tubulin displayed enhanced anti-cancer effects than single agents. These compounds further enrich the structural types of LSD1 inhibitors.