In vitro cellular potency of abrocitinib and human metabolites M1 and M2
| Cytokine-Induced pSTAT Assay | IC50/IC50,ua (nM) | |||||
|---|---|---|---|---|---|---|
| Cytokine | JAK Pair | pSTAT | Cell Assay | Abrocitinib | M1 | M2 |
| IL-4 | JAK1/JAK2 | pSTAT6 | Human keratinocytes | 77.0 | 433 | 134 |
| IL-13 | JAK1/JAK2 | pSTAT6 | Human keratinocytes | 81.9 | 236 | 84.1 |
| IL-22 | JAK1/TYK2 | pSTAT3 | Human keratinocytes | 420 | 703 | 198 |
| IL-31 | JAK1/JAK2 | pSTAT3 | IFNγ-primed THP-1 | 40.0 | 79.6 | 56.0 |
| TSLP | JAK1/JAK2 | pSTAT3 | hWB (CD3+ cells) | 1020/343 | 785/438 | 271/152 |
| IFNα | JAK1/TYK2 | pSTAT3 | hWB (lymphocytes) | 174/58.5 | 296/165 | 90.5/50.6 |
| IFNγ | JAK1/JAK2 | pSTAT1 | hWB (CD14+ cells) | 1690/569 | 1950/1090 | 2160/1210 |
| IL-6 | JAK1/JAK2 | pSTAT1 | hWB (CD3+ cells) | 343/115 | 171/95.3 | 136/76.0 |
| IL-12 | JAK2/TYK2 | pSTAT4 | hWB (lymphocytes) | 9730/3270 | 33,400/18,600 | 5170/2890 |
| IL-15 | JAK1/JAK3 | pSTAT5 | hWB (lymphocytes) | 537/181 | 558/311 | 353/197 |
| IL-21 | JAK1/JAK3 | pSTAT3 | hWB (lymphocytes) | 516/174 | 844/471 | 487/272 |
| IL-23 | JAK2/TYK2 | pSTAT3 | hWB (lymphocytes) | >16,500>5550 | 26,200/14,600 | 6210/3470 |
| IL-27 | JAK1/JAK2 | pSTAT3 | hWB (lymphocytes) | 228/76.7 | 382/213 | 234/131 |
| EPO | JAK2/JAK2 | pSTAT5 | hWB (spiked CD34+ cells) | 7180/2420 | 9750/5440 | 9470/5290 |
B/P, blood/plasma ratio; EPO, erythropoietin; hWB, human whole blood; IC50,u, unbound IC50; pSTAT, phospho-signal transducer and activator of transcription; TSLP, thymic stromal lymphopoietin.
ahWB IC50/IC50,u: total IC50/unbound IC50; unbound IC50 = hWB IC50 × (fu/B/P ratio); abrocitinib fu = 0.36; M1 fu = 0.63; M2 fu = 0.71; abrocitinib B/P = 1.07; M1 B/P = 1.13; M2 B/P = 1.27; mean IC50 from at least two experiments.