发现新型反苯环丙胺衍生物作为强效 LSD1 抑制剂。
Discovery of new tranylcypromine derivatives as highly potent LSD1 inhibitors.
机构信息
Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
出版信息
Bioorg Med Chem Lett. 2021 Jun 1;41:127993. doi: 10.1016/j.bmcl.2021.127993. Epub 2021 Mar 26.
Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.
曲马朵（TCP）结构修饰导致了新 LSD1 抑制剂的发现，其中化合物 26b 和 29b 分别有效地抑制 LSD1，IC 值分别为 17 和 11 nM，并且对 MAO-B 也具有良好的选择性。机制研究表明，化合物 29b 浓度依赖性地诱导 LSD1 过表达的 MGC-803 细胞中 H3K4me1/2 的积累，并且还抑制了 MGC-803 细胞的转移。总之，这两种化合物都可能是进一步研究的有前途的先导化合物。
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