Design and Synthesis of α-Ketoamides as Cathepsin S Inhibitors with Potential Applications against Tumor Invasion and Angiogenesis

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• 作者：Jo-Chun Chen ; Biing-Jiun Uang ; Ping-Chiang Lyu ; Jang-Yang Chang ; Ko-Jiunn Liu ; Ching-Chuan Kuo ; Hsing-Pang Hsieh ; Hsin-Chieh Wang ; Chao-Sheng Cheng ; Yi-Hsun Chang ; Margaret Dah-Tsyr Chang ; Wun-Shaing
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：June 10, 2010
• 年：2010
• 卷：53
• 期：11
• 页码：4545-4549
• 全文大小：811K
• 年卷期：v.53,no.11(June 10, 2010)
• ISSN：1520-4804

文摘

A series of small molecules bearing an α-ketoamide warhead were synthesized and evaluated for their ability to inhibit cathepsin S, a key proteolytic enzyme upregulated in many cancers during tumor progression and metastasis. Most of the synthetic compounds were noncytotoxic, but several robustly inhibited cathepsin S (IC₅₀ < 10 nM) and potently suppressed cell migration, invasion, and capillary tube formation. These results highlight the potential of α-ketoamide therapy for preventing or delaying cancer spread.