赖氨酸特异性脱甲基酶 (LSD)抑制剂

LSD (赖氨酸特异性脱甲基酶)是一种以FAD (黄素腺嘌呤二核苷酸)作为辅酶对组蛋白中甲基化赖氨酸进行脱甲基化的酶。LSD有两种异构体(LSD1, LSD2)。LSD1有望成为癌症的治疗靶点，而LSD2含有多种未知官能团，目前相关研究正在进行以阐明其功能^1-3)。LSD抑制剂 S1024 (1)和LSD抑制剂 S1025 (2)对LSD1表现出同等强度的抑制活性，而对LSD2表现出不同的抑制活性。1能通过抑制作用增加细胞内组蛋白修饰的H3K4me2⁴⁾。此外，可以利用1和2的活性差别来研究LSD2的功能。

关键词

B6490

LSD抑制剂 S1024

B6491

LSD抑制剂 S1025

P2908

反-2-苯基环丙胺盐酸盐

文献

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• 3) Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases
  • H. Niwa, T. Umehara, Epigenetics 2017, 12, 340.
• 4) Structure–Activity Relationship and In Silico Evaluation of cis- and trans-PCPA-Derived Inhibitors of LSD1 and LSD2
  • H. Niwa, C. Watanabe, S. Sato, T. Harada, H. Watanabe, R. Tabusa, S. Fukasawa, A. Shiobara, T. Hashimoto, O. Ohno, K. Nakamura, K. Tsuganezawa, A. Tanaka, M. Shirouzu, T. Honma, K. Matsuno, T. Umehara, ACS Med. Chem. Lett. 2022, 13, 1485.

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