| Description | Selective JAK3 inhibitor 1 is an irreversible JAK3 inhibitor with Ki values of 0.07 nM, 320 nM, 740 nM for JAK3, JAK1 and JAK2 respectively. It is also selective over the other kinases possessing a cysteine in the same region as JAK3, such as BMX, EGFR, ITK, and BTK. | ||||||
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| In vitro | Selective JAK3 inhibitor 1 is a potent inhibitor of JAK3 (IC50 = 0.15 nM) was 4300-fold selective for JAK3 over JAK1 in enzyme assays, 67-fold [interleukin (IL)-2 versus IL-6] or 140-fold [IL-2 versus erythropoietin or granulocyte-macrophage colony-stimulating factor (GMCSF)] selective in cellular reporter assays and >35-fold selective in human peripheral blood mononuclear cell assays (IL-7 versus IL-6 or GMCSF). The compound blocks cytokine signaling through JAK3, but not through other JAK family enzymes. It inhibits IL-7, IL-15, and IL-2 signaling in T cells, but does not inhibit any other cytokine signaling pathways[1]. | ||||||
| In vivo | Selective JAK3 inhibitor 1 has a partial effect on reversing inflammation and bone loss in the rat CIA model when administered therapeutically during the inflammatory phase of the model at doses that meet or exceed the exposure required for complete inhibition of the phenotype when dosed prophylactically. It inhibits leukocyte proliferation, but not erythrocyte proliferation in rats. Selective JAK3 inhibitor 1 could fully inhibit the development of inflammation[1]. |
