Evaluation of compound selectivity of aldo-keto reductases using differential scanning fluorimetry
Evaluation of compound selectivity of aldo-keto reductases using differential scanning fluorimetry
复制标题
使用差示扫描荧光法评估醛酮还原酶的化合物选择性
DOI：
10.1093/jb/mvw063
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发表时间：
2017
影响因子：
2.7
通讯作者：
and Yuji O. Kamatari
中科院分区：
文献类型：
--
作者：
Kabir Aurangazeb;Satoshi Endo;Naoki Toyooka;Mayuko Fukuoka;Kazuo Kuwata;and Yuji O. Kamatari
属于醛酮还原酶（AKR）超家族的AKR1B10抑制剂被认为是抗癌药物的有希望的候选者。AKR1B1是AKR1B10的一种结构相似的亚型，参与葡萄糖代谢。因此，选择性抑制AKR1B10是开发抗癌药物所必需的。在这项研究中，我们首先比较了熔融温度和50%的抑制浓度之间的相关性，分别从差示扫描荧光法（DSF）和酶抑制实验，并发现一个很好的相关性，除了低溶解度的化合物。该结果表明DSF方法可用于AKR超家族的药物筛选。然后，我们评估了它们作为针对所有七种主要人类AKR1家族蛋白的抑制剂的选择性，发现C18对AKR1B10最具特异性。
Inhibitors of AKR1B10 belonging to the aldo-keto reductase (AKR) superfamily are considered promising candidates for anti-cancer drugs. AKR1B1, a structurally similar isoform of AKR1B10, is involved in glucose metabolism. Thus, selective inhibition of AKR1B10 is required for the development of anti-cancer drugs. In this study, we first compared correlations between melting temperature and the 50% inhibition concentration obtained from differential scanning fluorimetry (DSF) and an enzyme inhibitory experiment, respectively, and a good correlation was found, except for compounds with low solubility. This result indicates that the DSF method is useful for drug screening for the AKR superfamily. We then evaluated their selectivity as inhibitors against all seven major human AKR1 family proteins and found that C18 is most specific for AKR1B10.