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

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 Wayne Chang, Chun Cheng Lin

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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 the potential of α-ketoamide therapy for preventing or delaying cancer spread.

Original languageEnglish
Pages (from-to)4545-4549
Number of pages5
JournalJournal of Medicinal Chemistry
Volume53
Issue number11
DOIs
Publication statusPublished - 2010 Jun 10

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Chen, J. C., Uang, B. J., Lyu, P. C., Chang, J. Y., Liu, K. J., Kuo, C. C., Hsieh, H. P., Wang, H. C., Cheng, C. S., Chang, Y. H., Chang, M. D. T., Chang, W. S. W., & Lin, C. C. (2010). Design and synthesis of α-ketoamides as cathepsin s inhibitors with potential applications against tumor invasion and angiogenesis. Journal of Medicinal Chemistry, 53(11), 4545-4549. https://doi.org/10.1021/jm100089e