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

doi:10.1021/jm100089e

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

Research output: Contribution to journal › Article › peer-review

59 Citations (Scopus)

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 language	English
Pages (from-to)	4545-4549
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	53
Issue number	11
DOIs	https://doi.org/10.1021/jm100089e
Publication status	Published - Jun 2010
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/jm100089e

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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

Chen, JC, Uang, BJ, Lyu, PC, Chang, JY, Liu, KJ, Kuo, CC, Hsieh, HP, Wang, HC, Cheng, CS, Chang, YH, Chang, MDT, Chang, WSW & Lin, CC 2010, 'Design and synthesis of α-ketoamides as cathepsin s inhibitors with potential applications against tumor invasion and angiogenesis', Journal of Medicinal Chemistry, vol. 53, no. 11, pp. 4545-4549. https://doi.org/10.1021/jm100089e

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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.",

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doi = "10.1021/jm100089e",

language = "English",

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AU - Chen, Jo Chun

AU - Uang, Biing Jiun

AU - Lyu, Ping Chiang

AU - Chang, Jang Yang

AU - Liu, Ko Jiunn

AU - Kuo, Ching Chuan

AU - Hsieh, Hsing Pang

AU - Wang, Hsin Chieh

AU - Cheng, Chao Sheng

AU - Chang, Yi Hsun

AU - Chang, Margaret Dah Tsyr

AU - Chang, Wun Shaing Wayne

AU - Lin, Chun Cheng

PY - 2010/6

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

Abstract

ASJC Scopus subject areas

UN SDGs

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