Table 1.
Suggested targets with impact on thrombosis and viral infection per JAK inhibitor drug and target prediction approach.
| Drug | Predicted target | Approach | Thrombosis | Viral infection/reactivation | |
|---|---|---|---|---|---|
| TIGER | SPiDER | ||||
| Baricitinib | Protein Kinase C Beta (PKC-β) | x | x | ||
| Adenosine Receptor A2A (AA2AR) | x | x | |||
| Inducible Nitric Oxide Synthase (iNOS) | x | x | |||
| Phosphodiesterase 10A (PDE10A) | x | x | x | ||
| Ras Related Protein Rab-7a | x | x | |||
| Epidermal growth factor receptor (EGFR) kinase | x | x | |||
| Deoxycytidine kinase (DCK) | x | x | |||
| Serine/threonine-protein kinase N2 (PKN2)a | x | x | |||
| Thymidine kinase (HSV)b | x | x | |||
| Tofacitinib | Arachidonate 15-Lipoxygenase (15-ALOX) | x | x | ||
| Adenosine Receptor A2A (AA2AR) | x | x | |||
| Short transient receptor potential channel 6 (TRPC6) | x | x | |||
| Short transient receptor potential channel 3 (TRPC3) | x | x | |||
| Adenosine Receptor A3 (ADORA3) | x | x | |||
| Exportin-1 (XPO1) | x | x | |||
| Serine/threonine-protein kinase N2 (PKN2) | x | x | x | ||
| Ubiquitin-conjugating enzyme E2 N (Ubc13) | x | x | |||
Commercial assays were unavailable for TRPC6 or TRPC3, and therefore, these targets could not be validated. Instead, transient receptor potential cation channel subfamily M member 6 (TRPM6) was employed for the respective binding assays.
aPKN2 was included in the list of targets tested for baricitinib, which allowed us to make a direct comparison between tofacitinib and baricitinib inhibitory activity on this target.
bHuman herpesvirus 1 (strain SC16).