Design and synthesis of α-ketoamides as cathepsin S inhibitors with potential applications against tumor invasion and angiogenesis

…, CC Kuo, HP Hsieh, HC Wang, CS Cheng…

Index: Chen, Jo-Chun; Uang, Biing-Jiun; Lyu, Ping-Chiang; Chang, Jang-Yang; Liu, Ko-Jiunn; Kuo, Ching-Chuan; Hsieh, Hsing-Pang; Wang, Hsin-Chieh; Cheng, Chao-Sheng; Chang, Yi-Hsun; Chang, Margaret Dah-Tsyr; Chang, Wun-Shaing Wayne; Lin, Chun-Cheng Journal of Medicinal Chemistry, 2010 , vol. 53, # 11 p. 4545 - 4549

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Citation Number: 24

Abstract

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 ...