核苷
运输机
化学
核苷转运体
鉴定(生物学)
班级(哲学)
计算生物学
组合化学
药理学
计算机科学
生物化学
医学
生物
基因
人工智能
植物
作者
Kazuya Tatani,Masahiro Hiratochi,Yoshinori Nonaka,Masayuki Isaji,Satoshi Shuto
摘要
Purine-rich foods have long been suspected as a major cause of hyperuricemia. We hypothesized that inhibition of human concentrative nucleoside transporter 2 (hCNT2) would suppress increases in serum urate levels derived from dietary purines. To test this hypothesis, the development of potent hCNT2 inhibitors was required. By modifying adenosine, an hCNT2 substrate, we successfully identified 8-aminoadenosine derivatives as a new class of hCNT2 inhibitors. Compound 12 moderately inhibited hCNT2 (IC50 = 52 ± 3.8 μM), and subsequent structure-activity relationship studies led to the discovery of compound 48 (IC50 = 0.64 ± 0.19 μM). Here we describe significant findings about structural requirements of 8-aminoadenosine derivatives for exhibiting potent hCNT2 inhibitory activity.
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