The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology area and beyond. Twenty years on, this article analyses the landscape of approved and investigational therapies that target kinases and trends within it, including the most popular targets of kinase inhibitors and their expanding range of indications. There are currently 71 small-molecule kinase inhibitors (SMKIs) approved by the FDA and an additional 16 SMKIs approved by other regulatory agencies. Although oncology is still the predominant area for their application, there have been important approvals for indications such as rheumatoid arthritis, and one-third of the SMKIs in clinical development address disorders beyond oncology. Information on clinical trials of SMKIs reveals that approximately 110 novel kinases are currently being explored as targets, which together with the approximately 45 targets of approved kinase inhibitors represent only about 30% of the human kinome, indicating that there are still substantial unexplored opportunities for this drug class. We also discuss trends in kinase inhibitor design, including the development of allosteric and covalent inhibitors, bifunctional inhibitors and chemical degraders.

FDA 于 2001 年批准伊马替尼是分子靶向癌症治疗的突破，并预示着激酶抑制剂的出现成为肿瘤学领域及其他领域的关键药物类别。20 年过去了，本文分析了针对激酶的已批准和正在研究的疗法的概况及其趋势，包括激酶抑制剂最流行的靶点及其不断扩大的适应症范围。目前有 71 种小分子激酶抑制剂 (SMKI) 获得 FDA 批准，另有 16 种 SMKI 获得其他监管机构批准。尽管肿瘤学仍然是其应用的主要领域，但类风湿性关节炎等适应症已获得重要批准，临床开发中有三分之一的 SMKI 解决了肿瘤学以外的疾病。SMKIs 临床试验的信息显示，目前正在探索大约 110 种新型激酶作为靶点，加上已批准的激酶抑制剂的大约 45 种靶点，仅占人类激酶组的 30% 左右，表明这方面仍有大量未开发的机会毒品类。我们还讨论了激酶抑制剂设计的趋势，包括变构和共价抑制剂、双功能抑制剂和化学降解剂的开发。