发现DS-1150b，一种新的激活GLUT4易位的杂蒽化合物

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-03-21 DOI:10.1016/j.bmcl.2025.130191

Masaki Meguro , Fuminao Doi , Tsuyoshi Soneda , Shinji Furuzono , Masahiro Konishi , Jun Harada , Jun Tanaka , Shinichi Inoue , Makoto Ono , Katsuji Kagechika

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引用次数: 0

摘要

葡萄糖转运蛋白4 （GLUT4）是一种高亲和力的葡萄糖转运蛋白，主要在骨骼肌、心肌和脂肪组织中表达，是胰岛素刺激的葡萄糖摄取的限速转运蛋白。增强骨骼肌GLUT4易位过程的化合物可能为2型糖尿病提供一种新的治疗方法。经过高通量筛选（HTS）和药物化学的努力，我们确定了杂蒽化合物DS-1150b（16·tBuNH2）是一种新的有效的GLUT4易位增强子。在Zucker脂肪大鼠模型中，DS-1150b可促进大鼠l6肌管中GLUT4的易位，并在口服葡萄糖耐量试验（oGTT）中显示出降血糖作用。同时简述了萘类似物DS20060511的鉴定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Discovery of DS-1150b, a novel xanthene compound for activating GLUT4 translocation

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Discovery of DS-1150b, a novel xanthene compound for activating GLUT4 translocation

The glucose transporter 4 (GLUT4) is a high-affinity glucose transporter that is predominantly expressed in the skeletal muscle, myocardium, and adipose tissue, and is the rate-limiting transporter of insulin-stimulated glucose uptake. Compounds that enhance the process of GLUT4 translocation in skeletal muscle would provide a novel treatment for type 2 diabetes mellitus. After a high-throughput screening (HTS) campaign and medicinal chemistry efforts, we identified the xanthene compound DS-1150b (16·tBuNH₂) as a novel potent GLUT4 translocation enhancer. DS-1150b was found to promote GLUT4 translocation in L6-myotubes in rats and showed a glucose-lowering effect in an oral glucose tolerance test (oGTT) in a Zucker fatty rat model. Identification of naphthalene analog DS20060511 is also briefly described.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.