tyk2 jh2

Deucravacitinib is a highly selective, orally bioavailable, allosteric TYK2 inhibitor for the treatment of autoimmune diseases. It blocks receptor-mediated Tyk2 activation by stabilizing the regulatory JH2 domain, inhibiting IL-12/23 and type I IFN pathways. It selectively binds to the TYK2 pseudokinase (JH2) domain with an IC50 of 1.0 nM.

TyK2-IN-2 is a selective inhibitor of TYK2 (IC50s: 7 nM, 0.1 μM, and 0.05 μM for TYK2 JH2, IL-23, and IFNα).

Tyk2-IN-5 is a selective and orally active inhibitor of Tyk2 JH2 (Ki: 0.086 nM for Tyk2 JH2; IC50: 25 nM for IFNα).

Tyk2-IN-7 is an inhibitor of TYK2 JH2, binds to the TYK2 JH2 domain (IC50: 0.00053 μM; Ki.app: 0.00007 μM).

NDI-034858 (TAK-279) is a tyrosine kinase 2 (TYK2) inhibitor (Kd<200 pM) that targets the JH2 structural domain of Tyk2 for the treatment of autoimmune diseases caused by aberrant expression of IL12 and IL23.

BMS-986202 is a novel Tyk2 inhibitor, binding to Tyk2 JH2, showing efficacies for IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus.

Tyk2-IN-16 is a potent and selective TYK2 inhibitor with an IC50 of less than 10 nM for TYK2-JH2. It inhibits pSTAT4 in NK92 cells with an IC50 of under 10 nM (WO2023220046A1; compound 184) [1].

Tyk2-IN-18 (compound 86), a potent inhibitor of tyrosine kinase 2 (Tyk2), effectively suppresses JAK2-JH2 with an IC 50 of ＜10 nM.

Tyk2-IN-9 (Compound 26), a selective Tyk-2 inhibitor, exhibits IC50 values of 0.076 nM for TYK2-JH2 and 1.8 nM for JAK1-JH2, respectively. This specificity makes it suitable for research into inflammatory or autoimmune diseases [1].

JAK1/TYK2-IN-5 (compound A1) is an inhibitor of JAK1 and TYK2, exhibiting Ki values of 0.0044 nM for TYK2JH2, 0.02 nM for JAK1 JH2, 6.9 μM for JAK1 JH1, 0.79 μM for JAK2 JH1, 0.21 μM for JAK3 JH1, and 0.55 μM for TYK2JH1. Additionally, it inhibits STAT activation mediated by TYK2/JAK1, induced by IFNα.

TYK2-IN-11 (Compound 5B) is a potent and selective inhibitor of Tyk-2, with IC50 values of 0.016 nM for TYK2-JH2 and 0.31 nM for JAK1-JH2. This compound shows potential for advancing research in inflammatory and autoimmune diseases [1].

Tyk2-IN-15 (Compound 97) is a selective inhibitor of tyrosine kinase 2 (Tyk2) with an IC50 value ≤ 10 nM for Tyk2-JH2. It is utilized in the research of inflammatory and autoimmune diseases [1].

Deucravacitinib-13C,d3 is a carbon-13 and deuterium labeled version of Deucravacitinib. Deucravacitinib (BMS-986165) is a highly efficient, selective, orally bioavailable allosteric TYK2 inhibitor with potential applications in autoimmune disease research. It selectively binds the TYK2 pseudokinase (JH2) domain (IC50=1.0 nM), blocking receptor-mediated Tyk2 activation by stabilizing the JH2 domain. Deucravacitinib inhibits the IL-12/23 and type I IFN pathways. Notably, Deucravacitinib is the first deuterated compound globally, designed de novo by the FDA, and is useful for studies in moderate to severe plaque psoriasis.