Table 1 CP-690,550 In Vitro Potency, Selectivity and Inhibition of Myeloid Progenitor Cell
Differentiation CP-690,550 Kinase InhibitionA | ||||||
|---|---|---|---|---|---|---|
Recombinant human kinase | Â | IC 50 (nM) | Â | K i (nM) | ||
JAK1 |  | 3.2 ± 1.4 |  | 0.68 ± 0.12 | ||
JAK2 |  | 4.1 ± 0.4 |  | 0.99 ± 0.04 | ||
JAK3 |  | 1.6 ± 0.2 |  | 0.24 ± 0.02 | ||
TYK2 |  | 34.0 ± 6.0 |  | 4.39 ± 0.27 | ||
CP-690,550 Inhibition of Cytokine Signaling in Human Whole Blood A | ||||||
Cytokine | JAK | pSTAT | CD3 + T cells IC 50 (nM) | Monocytes IC 50 (nM) | ||
IL-2 | 1/3 | 5 | 28 ± 5 | NA | ||
IL-4 | 1/3 | 6 | 50 ± 5 | NA | ||
IL-7 | 1/3 | 5 | 38 ± 9 | NA | ||
IL-6 | 1/2 | 1 | 54 ± 7 | NA | ||
IL-6 | 1/2 | 3 | 367 ± 49 | 406 ± 68 | ||
IFN-α | 1/TYK2 | 1 | 44 ± 4 | 148 ± 41 | ||
IFN-γ | 1/2 | 1 | NA | 178 ± 38 | ||
Species Comparison of CP-690,550 Inhibition of Cytokine Signaling in Whole Blood A | ||||||
Cytokine | JAK | pSTAT | Cells | Human IC 50 (nM) | Mouse IC 50 (nM) | Rat IC 50 (nM) |
IL-15 | 1/3 | 5 | CD8+ T cells | 56 ± 6 | 42 ± 12 | NA |
IL-21 | 1/3 | 3 | CD3+ T cells | 25 ± 6 | NA | 187 ± 48 |
IL-6 | 1/2 | 1 | CD3+ T cells | 54 ± 7 | 185 ± 46 | 62 ± 14 |
GM-CSF | 2 | 5 | Monocytes | 1377 ± 185 | 4379 ± 655 | 877 ± 171 |
CP-690,550 Inhibition of Human and Mouse Myeloid Progenitor Cell Differentiation B | ||||||
Total Human Myeloid Colonies IC 50 (nM) | Human CFU-G C Colonies IC 50 (nM) | Total Mouse Myeloid Colonies IC 50 (nM) | Mouse CFU-G Colonies IC 50 (nM) | |||
870 ± 120 | 930 ± 30 | 1210 ± 490 | 1128 ± 524 | |||