The specificity of JAK3 kinase inhibitors
| Autor: | David G. Perregaux, Perry S. Sawyer, Mark Edward Flanagan, Michael John Munchhof, Kelly S. Magnuson, Jonathan L. Doty, Craig R. Kent, Paul S. Changelian, Thomas M. Harris, Jianmin Sun, David A. Whipple, Cyrille Kuhn, Kudlacz Elizabeth M, Deborah J. Moshinsky |
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| Rok vydání: | 2008 |
| Předmět: |
Graft Rejection
Immunology Arthritis Biology Pharmacology Biochemistry Arthritis Rheumatoid In vivo medicine Humans Potency Pyrroles Enzyme Inhibitors Whole blood Clinical Trials as Topic Tofacitinib Kinase Janus Kinase 3 Cell Biology Hematology Protein-Tyrosine Kinases medicine.disease Transplant rejection Transplantation Kinetics Pyrimidines Quinazolines |
| Zdroj: | Blood. 111:2155-2157 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2007-09-115030 |
| Popis: | PF-956980 is a selective inhibitor of JAK3, related in structure to CP-690550, a compound being evaluated in clinical trials for rheumatoid arthritis and prevention of allograft rejection. PF-956980 has been evaluated against a panel of 30 kinases, and found to have nanomolar potency against only JAK3. Cellular and whole blood activity of this compound parallels its potency and selectivity in enzyme assays. It was effective in vivo at inhibiting the delayed type hypersensivity reaction in mice. We compared 2 commercially available JAK3 inhibitors (WHI-P131 and WHI-P154) in the same panel of biochemical and cellular assays and found them to be neither potent nor selective for JAK3. Both were found to be nanomolar inhibitors of the EGF receptor family of kinases. As these compounds have been used in numerous publications in the transplant and autoimmune disease literature, their specificity should be considered when interpreting these results. |
| Databáze: | OpenAIRE |
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