Ayala-Aguilera Cecilia C, Valero Teresa, Lorente-Macías Álvaro, Baillache Daniel J, Croke Stephen, Unciti-Broceta Asier
Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, United Kingdom.
J Med Chem. 2022 Jan 27;65(2):1047-1131. doi: 10.1021/acs.jmedchem.1c00963. Epub 2021 Oct 8.
The central role of dysregulated kinase activity in the etiology of progressive disorders, including cancer, has fostered incremental efforts on drug discovery programs over the past 40 years. As a result, kinase inhibitors are today one of the most important classes of drugs. The FDA approved 73 small molecule kinase inhibitor drugs until September 2021, and additional inhibitors were approved by other regulatory agencies during that time. To complement the published literature on clinical kinase inhibitors, we have prepared a review that recaps this large data set into an accessible format for the medicinal chemistry community. Along with the therapeutic and pharmacological properties of each kinase inhibitor approved across the world until 2020, we provide the synthesis routes originally used during the discovery phase, many of which were only available in patent applications. In the last section, we also provide an update on kinase inhibitor drugs approved in 2021.
激酶活性失调在包括癌症在内的进行性疾病病因中所起的核心作用，在过去40年里推动了药物发现项目的不断努力。因此，激酶抑制剂如今是最重要的药物类别之一。截至2021年9月，美国食品药品监督管理局（FDA）批准了73种小分子激酶抑制剂药物，在此期间其他监管机构也批准了更多抑制剂。为补充已发表的关于临床激酶抑制剂的文献，我们撰写了一篇综述，将这个庞大的数据集以一种便于药物化学界获取的形式进行了总结。除了截至2020年全球批准的每种激酶抑制剂的治疗和药理特性外，我们还提供了发现阶段最初使用的合成路线，其中许多仅在专利申请中可用。在最后一部分，我们还提供了2021年批准的激酶抑制剂药物的最新情况。
