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Nat Immunol. 2009 Apr;10(4):356-60. doi: 10.1038/ni.1701. Epub 2009 Mar 19.

Selectivity and therapeutic inhibition of kinases: to be or not to be?

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  • 1Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.


Protein kinases, which serve critical functions in signaling pathways in all cells, are popular therapeutic targets. At present, eight kinase inhibitors have been approved in the United States, each of which shows nanomolar potency. Although the initial goal was to generate inhibitors with a high degree of selectivity, recent experience has revealed that many of these approved compounds target more than one kinase. Surprisingly, this promiscuity is less problematic than one would have imagined; indeed, it opens new therapeutic opportunities. In this Perspective, we discuss the present status of Janus kinase inhibitors-a new class of immunosuppressive drugs-and the advantages and disadvantages of selectively inhibiting this class of kinase.

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