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PMID: 19295632 Published · ppublish English Journal Article Review

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

Nature immunology ·Vol. 10 ·No. 4 ·2009-04-00 ·Pages 356-60

Ghoreschi K, Laurence A, O'Shea JJ

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.

MeSH Terms
Antineoplastic Agents/adverse effects,therapeutic use Autoimmune Diseases/drug therapy,enzymology Humans Immunosuppressive Agents/adverse effects,therapeutic use Janus Kinases/antagonists & inhibitors,metabolism Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy,enzymology Phosphorylation Polycythemia Vera/drug therapy,enzymology Protein Kinase Inhibitors/therapeutic use Signal Transduction/physiology
Chemicals
Antineoplastic Agents Immunosuppressive Agents Protein Kinase Inhibitors Janus Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ghoreschi Kamran
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. ghoreschik@mail.nih.gov
Laurence Arian
O'Shea John J
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1701
Email
ghoreschik@mail.nih.gov
Published
2009-04-00
Epub
2009-00-19
Pages
356-60
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2758543
Subset
IM
Grants
Intramural NIH HHS · Z99 AR999999 · United States
External Links
PubMed source DOI: 10.1038/ni.1701 PMC Full Text View journal details
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