Design, synthesis, and biological evaluation of phenylcyclopropylamine-entinostat conjugates that selectively target cancer cells

被引：1

作者：

Ota, Yosuke ^{[1
]}

Itoh, Yukihiro ^{[1
,2
]}

Takada, Yuri ^{[2
]}

Yamashita, Yasunobu ^{[2
]}

Hu, Chenliang ^{[2
]}

Horinaka, Mano ^{[1
]}

Sowa, Yoshihiro ^{[1
]}

Masuda, Mitsuharu ^{[1
]}

Sakai, Toshiyuki ^{[1
]}

Suzuki, Takayoshi ^{[1
,2
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Mol Gastroenterol & Hepatol, 1-5 Shimogamohangi Cho,Sakyo Ku, Kyoto 6030823, Japan

[2] Osaka Univ, SANKEN, 8-1 Mihogaoka, Osaka, Ibaraki 5670047, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2024年 / 100卷

关键词：

Anticancer agent; Entinostat; Prodrug; LSD1; Targeted therapy; PHASE-I; INHIBITION;

D O I：

10.1016/j.bmc.2024.117632

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Small molecule-based selective cancer cell-targeting can be a desirable anticancer therapeutic strategy. Aiming to discover such small molecules, we previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) that selectively release anticancer agents in cancer cells where lysine-specific demethylase 1 (LSD1) is overexpressed. In this work, we designed PCPA-entinostat conjugates for selective cancer cell targeting. PCPAentinostat conjugate 12 with a 4-oxybenzyl group linker released entinostat in the presence of LSD1 in in vitro assays and selectively inhibited the growth of cancer cells in preference to normal cells, suggesting the potential of PCPA-entinostat conjugates as novel anticancer drug delivery small molecules.

引用

页数：7

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