Receptor tyrosine kinase signalling pathways have been successfully targeted to inhibit proliferation and angiogenesis for cancer therapy. However, kinase deregulation has been firmly demonstrated to play an essential role in virtually all major disease areas. Kinase inhibitor drug discovery programmes have recently broadened their focus to include an expanded range of kinase targets and therapeutic areas. In this Review, we provide an overview of the novel targets, biological processes and disease areas that kinase-targeting small molecules are being developed against, highlight the associated challenges and assess the strategies and technologies that are enabling efficient generation of highly optimized kinase inhibitors.

受体酪氨酸激酶信号通路已成功靶向抑制癌症治疗的增殖和血管生成。然而，已经证实激酶去调节在几乎所有主要疾病领域中都起着至关重要的作用。激酶抑制剂药物发现计划最近扩大了其关注范围，以扩大激酶靶标和治疗领域的范围。在本综述中，我们概述了针对激酶的小分子正在针对的新型靶标，生物学过程和疾病领域，重点介绍了相关挑战，并评估了能够高效产生高度优化的激酶抑制剂的策略和技术。