Stazi Giulia, Zwergel Clemens, Valente Sergio, Mai Antonello
a Dipartimento di Chimica e Tecnologie del Farmaco , Sapienza Università di Roma , Rome , Italy.
b Istituto Pasteur-Fondazione Cenci Bolognetti , Sapienza Università di Roma , Rome , Italy.
Expert Opin Ther Pat. 2016 May;26(5):565-80. doi: 10.1517/13543776.2016.1165209. Epub 2016 Mar 28.
Lysine demethylase 1 (LSD1) plays an important role in mediating the expression of genes involved in cancer and non-cancer diseases such as viral infections, cardiovascular and neurodegenerative disorders. It is involved in a number of processes from adipogenesis to cell adhesion to viral latency, regulating several cell pathways related with proliferation, development, and cell cycle control. Numerous chemical entities have been studied in recent years and some of them entered the clinical arena.
This review summarizes recent efforts in the drug development of LSD1 inhibitors reported in the patent literature covering the 2010-2015 period, including their potential use as therapeutics in cancerous, neurological, inflammatory, cardiovascular, and viral diseases.
The development of novel potent and selective LSD1 inhibitors is ongoing, in order to improve their potency and selectivity against specific types of cancer or non-cancer diseases. More in-depth studies are required to assess the role of LSD1 inhibitors in the expression of LSD1 target genes, for a better assessment of the biochemistry underlying their efficacy, and to provide evidence for any possible side effects. Furthermore, an interesting therapeutic approach is the use of LSD1 inhibitors in conjunction with other epidrugs to combine their therapeutic potential, leading to innovative, personalized treatments.
赖氨酸去甲基化酶1（LSD1）在介导参与癌症和非癌症疾病（如病毒感染、心血管疾病和神经退行性疾病）的基因表达中发挥着重要作用。它参与了从脂肪生成到细胞黏附再到病毒潜伏的多个过程，调节着与增殖、发育和细胞周期控制相关的多个细胞途径。近年来，人们对许多化学实体进行了研究，其中一些已进入临床阶段。
本综述总结了2010 - 2015年专利文献中报道的LSD1抑制剂药物研发的最新进展，包括它们在癌症、神经、炎症、心血管和病毒疾病治疗中的潜在用途。
新型强效和选择性LSD1抑制剂的研发正在进行中，以提高它们对特定类型癌症或非癌症疾病的效力和选择性。需要更深入地研究来评估LSD1抑制剂在LSD1靶基因表达中的作用，以便更好地评估其疗效背后的生物化学机制，并为任何可能的副作用提供证据。此外，一种有趣的治疗方法是将LSD1抑制剂与其他表观遗传药物联合使用，以结合它们的治疗潜力，从而实现创新的个性化治疗。
