title: Design and synthesis of alpha-ketoamides as cathepsin S inhibitors with potential applications against tumor invasion and angiogenesis.
abstract: A series of small molecules bearing an alpha-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 (IC(50) < 10 nM) and potently suppressed cell migration, invasion, and capillary tube formation. These results highlight the potential of alpha-ketoamide therapy for preventing or delaying cancer spread.
authors.affiliation: Department of Chemistry, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
authors.forename: Jo-Chun
authors.initials: JC
authors.lastname: Chen
authors.forename: Biing-Jiun
authors.initials: BJ
authors.lastname: Uang
authors.forename: Ping-Chiang
authors.initials: PC
authors.lastname: Lyu
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.forename: Ko-Jiunn
authors.initials: KJ
authors.lastname: Liu
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Wang
authors.forename: Chao-Sheng
authors.initials: CS
authors.lastname: Cheng
authors.forename: Yi-Hsun
authors.initials: YH
authors.lastname: Chang
authors.forename: Margaret Dah-Tsyr
authors.initials: MD
authors.lastname: Chang
authors.forename: Wun-Shaing Wayne
authors.initials: WS
authors.lastname: Chang
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation
chemical_list: D000577:Amides; D011480:Protease Inhibitors; D002403:Cathepsins; C028217:cathepsin S