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Table 1 CP-690,550 In Vitro Potency, Selectivity and Inhibition of Myeloid Progenitor Cell

From: Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis

Differentiation CP-690,550 Kinase InhibitionA
Recombinant human kinase   IC 50 (nM)   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
  1. A Dose-response data were fit using four parameter logistic equations to determine IC50, and represent the mean ± SEM from at least three independent studies. Inhibition constants (Ki) were determined by measuring initial velocities for each enzyme in the presence of varying MgATP and inhibitor concentrations. NA (not applicable), signaling through the indicated cytokines was insufficient to determine inhibition. B IC50 values were derived from the Boltzman Fit Model and represent the mean ± (standard deviation, SD); C CFU-G = colony forming units - granulocytes.