Small molecule

Bioinformatics

Biology

Receptor tyrosine kinase

Kinase

Signal transduction

Computational biology

Drug discovery

Cell biology

Tyrosine kinase

Cancer research

Biochemistry

Medicine

Nature Reviews Drug Discovery

Existing kinase inhibitor drugs predominantly target receptor tyrosine kinases in cancer. Here, Gray and Ferguson review novel kinase targets in oncology, degenerative diseases, inflammatory disorders and infectious diseases. Advances in medicinal chemistry, selectivity profiling and computer-aided drug design, which are enabling the design of improved kinase inhibitors, are discussed. 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.

Kinase inhibitors: the road ahead