Daub Henrik
Evotec (München) GmbH , Am Klopferspitz 19a, 82152 Martinsried, Germany.
ACS Chem Biol. 2015 Jan 16;10(1):201-12. doi: 10.1021/cb5008794. Epub 2014 Dec 17.
Small molecule inhibitors of protein kinases are key tools for signal transduction research and represent a major class of targeted drugs. Recent developments in quantitative proteomics enable an unbiased view on kinase inhibitor selectivity and modes of action in the biological context. While chemical proteomics techniques utilizing quantitative mass spectrometry interrogate both target specificity and affinity in cellular extracts, proteome-wide phosphorylation analyses upon kinase inhibitor treatment identify signal transduction pathway and network regulation in an unbiased manner. Thus, critical information is provided to promote new insights into mechanisms of kinase signaling and their relevance for kinase inhibitor drug discovery.
蛋白激酶的小分子抑制剂是信号转导研究的关键工具，也是一大类靶向药物。定量蛋白质组学的最新进展使人们能够在生物学背景下对激酶抑制剂的选择性和作用模式有一个无偏见的认识。利用定量质谱的化学蛋白质组学技术可在细胞提取物中研究靶点特异性和亲和力，而激酶抑制剂处理后的全蛋白质组磷酸化分析则能以无偏见的方式识别信号转导途径和网络调控。因此，这些关键信息有助于推动对激酶信号传导机制及其与激酶抑制剂药物发现相关性的新认识。
