Tyk2-IN-3

Tyk2-IN-3 is a Tyk2 pseudokinase inhibitor, with an IC₅₀ of 485 nM. IC50 & Target: IC50: 485 nM (Tyk2)^[1]. In Vivo: Tyk2-IN-3 (compound 1) is very potent against the Tyk2 pseudokinase (99% inhibition at 1 μM) but lacks potency against all other kinases in the kinome assay panel except IKK (96% inhibition) and the JAK1 pseudokinase domain (99% inhibition at 1 μM). No evidence of binding to the catalytic domain of Tyk2 or any other JAK family kinase is evident at 1 μM, and subsequent enzymatic assays confirm the lack of activity against purified catalytic domains (IC₅₀>>2 μM). The pseudokinase domains of JAK2 and JAK3 are not part of the kinome screening panel. In the IL-23-stimulated kit225 T cell assay, Tyk2-IN-3 inhibits the stimulated response with an IC₅₀ of 485±143 nM (n=3)^[1].