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Kling, Andreas; Jantos, Katja; Mack, Helmut; Hornberger, Wilfried; Drescher, Karla; Nimmrich, Volker; Relo, Ana; Wicke, Karsten; Hutchins, Charles W; Lao, Yanbin; Marsh, Kennan; Moeller, Achim
Journal of medicinal chemistry, 08/2017, Letnik: 60, Številka: 16Journal Article
Calpain overactivation has been implicated in a variety of pathological disorders including ischemia/reperfusion injury, cataract formation, and neurodegenerative diseases such as Alzheimer’s disease (AD). Herein we describe our efforts leading to the identification of ketoamide-based 2-(3-phenyl-1H-pyrazol-1-yl)nicotinamides as potent and reversible inhibitors of calpain with high selectivity versus related cysteine protease cathepsins, other proteases, and receptors. Broad efficacy in a set of preclinical models relevant to AD suggests that inhibition of calpain represents an attractive approach with potential benefit for the treatment of AD.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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