{"title":"Temperature does matter-an additional dimension in kinase inhibitor development.","authors":"Miriam Strauch, Florian Heyd","doi":"10.1111/febs.15564","DOIUrl":null,"url":null,"abstract":"<p><p>Kinase inhibitors are a major focus in drug development. Recent work shows that subtle temperature changes in the physiologically relevant temperature range can dramatically alter kinase activity and specificity. We argue that temperature is an essential factor that should be considered in inhibitor screening campaigns. In many cases, high-throughput screening is performed at room temperature or 30 °C, which may lead to many false positives and false negatives when evaluating potential inhibitors in the physiological temperature range. As one example, we discuss a new antimalaria compound that inhibits the highly temperature-sensitive kinase CLK3 (CDC2-like kinase 3) from Plasmodium falciparum.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 10","pages":"3148-3153"},"PeriodicalIF":5.5000,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15564","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/febs.15564","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/9/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 2
Abstract
Kinase inhibitors are a major focus in drug development. Recent work shows that subtle temperature changes in the physiologically relevant temperature range can dramatically alter kinase activity and specificity. We argue that temperature is an essential factor that should be considered in inhibitor screening campaigns. In many cases, high-throughput screening is performed at room temperature or 30 °C, which may lead to many false positives and false negatives when evaluating potential inhibitors in the physiological temperature range. As one example, we discuss a new antimalaria compound that inhibits the highly temperature-sensitive kinase CLK3 (CDC2-like kinase 3) from Plasmodium falciparum.
期刊介绍:
The FEBS Journal is an international journal devoted to the rapid publication of full-length papers covering a wide range of topics in any area of the molecular life sciences. The criteria for acceptance are originality and high quality research, which will provide novel perspectives in a specific area of research, and will be of interest to our broad readership.
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