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

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

Abstract

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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / enzymology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Phosphorylation
  • Polycythemia Vera / drug therapy
  • Polycythemia Vera / enzymology
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / physiology

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Protein Kinase Inhibitors
  • Janus Kinases