Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors

被引：19

作者：

Huang, Shih-Chung ^{[1
]}

Adhikari, Sharmila ^{[1
]}

Brownell, James E. ^{[1
]}

Calderwood, Emily F. ^{[1
]}

Chouitar, Jouhara ^{[1
]}

D'Amore, Natalie Roy ^{[1
]}

England, Dylan B. ^{[1
]}

Foley, Klaudia ^{[1
]}

Harrison, Sean J. ^{[1
]}

LeRoy, Patrick J. ^{[1
]}

Lok, David ^{[1
]}

Lublinsky, Anna ^{[1
]}

Ma, Li-Ting ^{[1
]}

Menon, Saurabh ^{[1
]}

Yang, Yu ^{[1
]}

Zhang, Ji ^{[1
]}

Gould, Alexandra E. ^{[1
]}

机构：

[1] Takeda Pharmaceut Int Co, 40 Landsdowne St, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2020年 / 28卷 / 19期

关键词：

E1; enzyme; ATG7; inhibitor; Autophagy; AUTOPHAGY; UBIQUITIN;

D O I：

10.1016/j.bmc.2020.115681

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：

Autophagy is postulated to be required by cancer cells to survive periods of metabolic and/or hypoxic stress. ATG7 is the E1 enzyme that is required for activation of Ubl conjugation pathways involved in autophagosome formation. This article describes the design and optimization of pyrazolopyrimidine sulfamate compounds as potent and selective inhibitors of ATG7. Cellular levels of the autophagy markers, LC3B and NBR1, are regulated following treatment with these compounds.

引用

页数：21

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