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T Fukuda, R Goto, T Kiho, K Ueda, S Muramatsu, M Hashimoto, A Aki, K Watanabe and N Tanaka
Abstract
Hepcidin has emerged as the central regulatory molecule in systemic iron homeostasis, and its inhibition could be a favorable strategy for treating anemia of chronic disease (ACD). Here, we report the design, synthesis and structure-activity relationships (SAR) of a series of 4,6-disubstituted indazole compounds as hepcidin production inhibitors. The optimization study of multi-kinase inhibitor 1 led to the design of a potent and bioavailable hepcidin production inhibitor, 32 (DS28120313), which showed serum hepcidin-lowering effects in an interleukin-6-induced acute inflammatory mouse model.
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Concepts
Xanthine oxidase inhibitor, Acute, Hepcidin, Enzyme inhibitor, Chronic, Inhibitor, Anemia of chronic disease, Human iron metabolism
MeSH headings
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