Identification of a novel boronic acid as a potent,selective, and orally active hormone sensitive lipase inhibitor |
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Institution: | 1. Department of Orthopedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan;2. Department of Orthopedic Biomaterial Science, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan |
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Abstract: | Hormone sensitive lipase (HSL) is an attractive therapeutic target of dyslipidemia. We designed and synthesized several compounds as reversible HSL inhibitors with a focus on hydrophobic interactions, which was thought to be effective upon the HSL inhibitory activity. In these efforts, we identified boronated compound 12 showing a potent HSL inhibitory activity with an IC50 value of 7 nM and a high selectivity against cholinesterases. Furthermore, compound 12 is the first boron containing HSL inhibitor that has shown an antilipolytic effect in rats after oral administration at 3 mg/kg. |
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Keywords: | Hormone sensitive lipase (HSL) Dyslipidemia Lipolysis Boronic acid |
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