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[期刊论文]
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Pharmacological characterization of the selective 11β-hydroxysteroid dehydrogenase 1 inhibitor, BI 135585, a clinical candidate for the treatment of type 2 diabetes
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作 者：
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Bradford S. Hamilton;Frank Himmelsbach;Herbert Nar;Annette Schuler-Metz;Paula Krosky;Joan Guo;Rong Guo;Shi Meng;Yi Zhao;Deepak S. Lala;Linghang Zhuang;David A. Claremon;Gerard M. McGeehan;
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出版年：2015
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页 码：50 - 55
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出版社：Elsevier BV
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摘 要：
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To combat the increased morbidity and mortality associated with the developing diabetes epidemic new therapeutic interventions are desirable. Inhibition of intracellular cortisol generation from cortisone by blocking 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been shown to ameliorate the risk factors associated with the metabolic syndrome. A challenge in developing 11β-HSD1 inhibitors has been the species selectivity of small molecules, as many compounds are primate specific. Here we describe our strategy to identify potent selective 11β-HSD1 inhibitors while ensuring target engagement in key metabolic tissues, liver and fat. This strategy enabled the identification of the clinical candidate, BI 135585.
Copyright © 2014 Elsevier B.V. All rights reserved.
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关键字：
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11@b-Hydroxysteroid dehydrogenase 1
; Inhibitor
; Type 2 diabetes
; Adipose tissue
; Liver
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所属期刊
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ISSN: 0014-2999
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来自：Elsevier BV
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