Table 2.
Type I cytokine receptor | Type II cytokine receptor | |||||||
Receptor family | GP-130 family | IL-2R CGC family | IL-12/23 family | CβC family | IL-10 family | Type I IFNs | Type II IFNs | |
Cytokine ligands | IL-6, 11, 27, LIF, OSM | IL-2, 4, 7, 9, 15, 21 | IL-12, 23 | IL-3, IL-5, GM-CSF | IL-10, 19, 20, 22, 26 | IFNα, β | IFNγ | |
Asc JAKs | JAK1, JAK2, TYK2 | JAK1, JAK3 | JAK2, TYK2 | JAK2 | JAK1, JAK2, TYK2 | JAK1, TYK2 | JAK1, JAK2 | |
Downstream STATs | STAT1, 3, 5 | STAT1, 3, 5, (6) | STAT3, 4 | STAT5 | STAT1, 3, 5 | STAT1, 2, 3 | STAT1, 3, 5 | |
Inhibitors in increasing order of selectivity | Tofacitinib | +++ | +++ | +++ | +++ | +++ | +++ | +++ |
Peficitinib | +++ | +++ | ++ | ++ | +++ | +++ | +++ | |
Baricitinib | +++ | +++ | +++ | +++ | +++ | +++ | +++ | |
Upadacitinib | +++ | +++ | ++ | + | +++ | +++ | +++ | |
Filgotinib | +++ | +++ | + | + | +++ | +++ | +++ | |
Abrocitinib | +++ | +++ | – | – | +++ | +++ | +++ |
The degree of inhibition is normalised against the ability of each JAKinib to inhibit JAK1 as measured by the IC50 value in nM.
+++=IC50 of the most inhibited associated JAK for a given cytokine family is lower than or equal to the IC50 for JAK1.
++=IC50 of the most inhibited associated JAK for a given cytokine family is onefold to twofold higher than the IC50 for JAK1.
+=IC50 of the most inhibited associated JAK for a given cytokine family is 2-fold to 10-fold higher than the IC50 for JAK1.
–=IC50 of the most inhibited associated JAK for a given cytokine family is >10 times higher than the IC50 for JAK1.
GM-CSF, granulocyte macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; JAK, Janus kinase; STAT, signal transducer and activator of transcription.