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Kinase drug discovery 20 years after imatinib
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Dysregulated kinase signalling is implicated in various processes of carcinogenesis and is also pathologically involved in many other diseases, including autoimmune and inflammatory diseases, degenerative disorders and infectious diseases. Protein kinases therefore represent an important class of drug targets, particularly in the field of oncology. However, exploitation of the full potential of kinases as drug targets has been limited by several challenges, particularly low potency, poor specificity and the development of drug resistance.
Following the landmark approval of the first kinase inhibitor imatinib in 2001 for the treatment of chronic myeloid leukaemia, significant advances in the field have led to over 70 kinase inhibitors gaining approval, transforming the clinical care of multiple malignancies and targeting a handful of other disorders.
This poster from Nature Reviews Drug Discovery illustrates key advances that have been made in the development of potent and specific kinase inhibitor therapies over the last 20 years, including the increased molecular and structural understanding of human kinases, the emergence of strategies to combat resistance to kinase inhibitors in cancer therapy, recognition of the potential of combination therapies, and the application of kinase inhibitors beyond cancer.
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Cohen, P., Cross, D. & Jänne, P.A. Kinase drug discovery 20 years after imatinib. Nat Rev Drug Discov (2022). https://doi.org/10.1038/s41573-022-00418-2
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DOI: https://doi.org/10.1038/s41573-022-00418-2