Bioorganic and Medicinal Chemistry p. 775 - 785 (2018)
Update date:2022-08-12
Topics:
Ota, Yosuke
Miyamura, Shin
Araki, Misaho
Itoh, Yukihiro
Yasuda, Shusuke
Masuda, Mitsuharu
Taniguchi, Tomoyuki
Sowa, Yoshihiro
Sakai, Toshiyuki
Itami, Kenichiro
Yamaguchi, Junichiro
Suzuki, Takayoshi
Lysine-specific demethylase 1 (LSD1) is an attractive molecular target for cancer therapy. We have previously reported potent LSD1-selective inhibitors (i.e., NCD18, NCD38, and their analogs) consisting of trans-2-phenylcyclopropylamine (PCPA) or trans-2-arylcyclopropylamine (ACPA) and a lysine moiety that could form a γ-turn structure in the active site of LSD1. Herein we report the design, synthesis and evaluation of γ-turn mimetic compounds for further improvement of LSD1 inhibitory activity and anticancer activity. Among a series of γ-turn mimetic compounds synthesized by a Mitsunobu-reaction-based amination strategy, we identified 1n as a potent and selective LSD1 inhibitor. Compound 1n induced cell cycle arrest and apoptosis through histone methylation in human lung cancer cells. The γ-turn mimetics approach should offer new insights into drug design for LSD1-selective inhibitors.
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Doi:10.1016/j.jcat.2011.12.007
(2012)Doi:10.1002/aoc.4942
(2019)Doi:10.1016/j.steroids.2010.05.012
(2010)Doi:10.1080/10426500490484995
(2004)Doi:10.1039/c6cp06864b
(2017)Doi:10.1039/d0ra04110f
(2020)