Table 1.
Inhibitory potency for TD-1473 and tofacitinib with respect to cytokine-induced pSTAT, IL-8 or IFNγ elevation in human epithelial cells, monocytes, PBMCs or whole blood
| Cell type | Cytokine stimulus/end point | JAK pairing | Mean ± SD inhibitory potency [pIC50] | |
|---|---|---|---|---|
| TD-1473 | Tofacitinib | |||
| Human epithelial cells [HT-29] | IL-13/pSTAT6 | JAK1/JAK2 | 7.1 ± 0.2 [n = 9] | 7.3 ± 0.1 [n = 14] |
| IL-13/IL-8 | JAK1/JAK2 | 7.1 ± 0.3 [n = 4] | 7.6 ± 0.2 [n = 12] | |
| Human monocytes [THP1] | IL-4/pSTAT6 | JAK1/JAK3 | 7.5 ± 0.1 [n = 2] | 7.4 ± 0.1 [n = 12] |
| IL-6/pSTAT3 | JAK1/JAK2 | 7.3 ± 0.0 [n = 2] | 7.5 ± 0.1 [n = 10] | |
| GM-CSF/pSTAT5 | JAK2/JAK2 | 7.0 ± 0.1 [n = 2] | 6.8 ± 0.1 [n = 4] | |
| Human PBMCs [T cells] | IL-2 [+ anti-CD3]/pSTAT5 | JAK1/JAK3 | 7.5 ± 0.4 [n = 5] | 7.7 ± 0.3 [n = 5] |
| IL-4/pSTAT6 | JAK1/JAK3 | 7.5 ± 0.3 [n = 8] | 7.8 ± 0.3 [n = 8] | |
| IL-6/pSTAT3 | JAK1/JAK2 | 7.1 ± 0.3 [n = 4] | 7.2 ± 0.3 [n = 4] | |
| IFNα/pSTAT1 | JAK1/TYK2 | 7.5 ± 0.1 [n = 6] | 7.5 ± 0.2 [n = 6] | |
| GM-CSF/pSTAT5 | JAK2/JAK2 | 7.2 ± 0.3 [n = 2] | 6.6 ± 0.2 [n = 3] | |
| IL-12/pSTAT4 | JAK2/TYK2 | 6.9 ± 0.1 [n = 4] | 5.9 ± 0.2 [n = 4] | |
| IL-2 [+ anti-CD3]/IFNγ | JAK1/JAK3 | 7.2 ± 0.3 [n = 8] | 7.5 ± 0.3 [n = 8] | |
| Human whole blood | GM-CSF/pSTAT5 | JAK2/JAK2 | 6.7 ± 0.4 [n = 4] | 6.9 ± 0.4 [n = 4] |
| Mouse colonic epithelial cells | IL-6/pSTAT1 | JAK1/JAK2 | 7.3 ± 0.0 [n = 2] | 7.9 ± 0.3 [n = 3] |
| IFNα/pSTAT1 | JAK1/TYK2 | 6.8 ± 0.1 [n = 2] | 6.7 ± 0.1 [n = 3] | |
| IFNγ/pSTAT1 | JAK1/JAK2 | 7.0 ± 0.1 [n = 2] | 6.9 ± 0.0 [n = 3] | |
CD, cluster of differentiation; GM-CSF, granulocyte-monocyte colony stimulating factor; JAK, Janus kinase; IFN, interferon; IL, interleukin; PBMCs, peripheral blood mononuclear cells; pIC50, −log10 concentration producing 50% maximal inhibition; pSTAT, phosphorylated signal transducer and activator of transcription; SD, standard deviation; TYK, tyrosine kinase 2.