Crystal structure of TYK2 kinase with compound 19

Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1.

Non-receptor tyrosine-protein kinase TYK2

MAHHHHHHHHHHGALEVLFQGPGDPTVFHKRYLKKIRDLGEGHFGKVSLYCYDPTNDGTGEMVAVKALKADAGPQHRSGW
KQEIDILRTLYHEHIIKYKGCCEDAGAASLQLVMEYVPLGSLRDYLPRHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDL
AARNVLLDNDRLVKIGDFGLAKAVPEGHE(PTR)YRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCDS
SQSPPTKFLELIGIAQGQMTVLRLTELLERGERLPRPDKCPAEVYHLMKNCWETEASFRPTFENLIPILKTVHEKYQGQA
PS

MAHHHHHHHHHHGALEVLFQGPGDPTVFHKRYLKKIRDLGEGHFGKVSLYCYDPTNDGTGEMVAVKALKADAGPQHRSGW
KQEIDILRTLYHEHIIKYKGCCEDAGAASLQLVMEYVPLGSLRDYLPRHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDL
AARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSSQSP
PTKFLELIGIAQGQMTVLRLTELLERGERLPRPDKCPAEVYHLMKNCWETEASFRPTFENLIPILKTVHEKYQGQAPS

kinase, TRANSFERASE, TRANSFERASE-INHIBITOR complex

DPTVFHKRYLKKIRDLGEGHFGKVSLYCYDPTNDGTGEMVAVKALKADCGPQHRSGWKQEIDILRTLYHEHIIKYKGCCE
DQGEKSLQLVMEYVPLGSLRDYLPRHSIGLAQLLLFAQQICEGMAYLHAQHYIHRDLAARNVLLDNDRLVKIGDFGLAKA
VPEGHEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSSQSPPTKFLELIGIAQGQMTVLRLTEL
LERGERLPRPDKCPCEVYHLMKNCWETEASFRPTFENLIPILKTVHEKYQGQAPS