Deucravacitinib is very potent and selective allosteric inhibitor of tyrosine kinase 2 (TYK2). It binds to and is selective for the TYK2 pseudokinase domain (JH2, IC50 = 0.2 nM), with no activity against canonical JH1 domain of TYK2, JAK1,2, or 3.1 It is 5-fold less active against the JAK1 JH2 domain (IC50 = 1 nM). Deucravacitinib blocked signaling and functional responses in human TH17, TH1, B cells, and myeloid cells and displayed robust efficacy in vitro and in vivo in autoimmune disease animal models.2
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