Laboratory of RNA Biochemistry, Institute of Chemistry and Biochemistry, Freie Universitaet Berlin, Germany.
FEBS J. 2021 May;288(10):3148-3153. doi: 10.1111/febs.15564. Epub 2020 Sep 26.
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.
激酶抑制剂是药物开发的重点。最近的研究表明，在生理相关温度范围内的微小温度变化可以显著改变激酶的活性和特异性。我们认为，温度是抑制剂筛选过程中应考虑的一个重要因素。在许多情况下，高通量筛选是在室温或 30°C 下进行的，这可能导致在评估生理温度范围内的潜在抑制剂时出现许多假阳性和假阴性。作为一个例子，我们讨论了一种新的抗疟化合物，它可以抑制来自恶性疟原虫的高度温度敏感的激酶 CLK3（CDC2 样激酶 3）。
