Table 1.
In vitro potency of upadacitinib
| Recombinant Human Kinase | IC50 nM | Fold selectivity vs. JAK1 | ||
|---|---|---|---|---|
| in Biochemical AssaysA | ||||
| JAK1 | 47 +/− 6.1 | 1 | ||
| JAK2 | 120 +/− 29.6 | 2.5 | ||
| JAK3 | 2304 +/− 380.3 | 49 | ||
| TYK2 | 4690 | 100 | ||
| Engineered Cellular Assays | ||||
| Ba/F3 Cellular | IC50 nM | Fold selectivity vs. JAK1 | ||
| JAK1 | 14 | 1 | ||
| JAK2 | 593 +/− 118.7 | 42 | ||
| JAK3 | 1860 +/−207.2 | 133 | ||
| TYK2 | 2715 +/− 548.7 | 194 | ||
| Cytokine Signaling in Human Cells | ||||
| Cytokine | JAK | pSTAT | Cells | Human IC50 nM |
| IL-6 | 1 | 3 | TF-1 | 11 +/− 1.3 |
| IL-6 | 1 | 3 | CD14+ whole blood | 78 +/− 0.3 |
| IL-6 | 1 | 3 | CD3+ whole blood | 207 +/− 9 |
| OSM | 1 | 3 | TF-1 | 1.6 N = 2 |
| Epo | 2 | 5 | UT7 | 649 +/− 41.2 |
| IL-2 | 1/3 | 5 | T-blasts | 10 +/− 1.1 |
| IL-15 | 1/3 | 5 | T-blasts | 22 +/−6.7 |
| IFNγ | 1/2 | 1 | CD14+ monocytes | 19 |
| IL-4 | 1/3 | 6 | HEKa B | 2 |
| IL-13 | 1/TYK2 | 6 | HEKa | 4 |
| IL-31 | 1/2 | 3 | HEKa | 3 |
aEnzyme reactions were conducted at 0.1 mM ATP. IC50 values represent the mean +/− SEM from at least three independent studies except where noted. B HEKa = human epithelial keratinocytes, adult