mProX™ Human TYK2 Stable Cell Line

Torp Jensen, Lise. et al. "Allosteric TYK2 inhibition: redefining autoimmune disease therapy beyond JAK1-3 inhibitors." EBioMedicine, 2023.
The impact of JAK inhibitors on multiple cytokine pathways has been recognized for their high efficacy in treating complex diseases, such as cancers and immune-mediated disorders. However, the broad reach of these inhibitors has raised safety concerns, leading to a demand for more selective options. Deucravacitinib, a first-in-class allosteric TYK2 inhibitor, has advanced the field significantly. Unlike traditional JAK1-3 inhibitors that compete at kinase domain catalytic sites, deucravacitinib targets the regulatory pseudokinase domain of TYK2. This approach resembles the functional effect of a naturally occurring TYK2 variant, P1104A, which protects against multiple autoimmune diseases while still allowing for sufficient TYK2-mediated cytokine signaling to prevent immune deficiency. With its unprecedentedly high functional selectivity and efficacy-safety profile, initially demonstrated in psoriasis and supported by genetic evidence, deucravacitinib has shown promising results in early clinical trials for systemic lupus erythematosus. As a result, this inhibitor is a promising candidate for exploration in other autoimmune diseases that require safe and effective treatments.
Torp Jensen, Lise. et al. "Allosteric TYK2 inhibition: redefining autoimmune disease therapy beyond JAK1-3 inhibitors." EBioMedicine, 2023.
Pubmed: 37863021   DOI: 10.1016/j.ebiom.2023.104840

Gracias, Ségolène, et al. "Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2." EMBO reports (2023): e57424.
The interaction between flaviviruses and interferons and how it is used to avoid antiviral functions is not fully understood. Different virological approaches were employed to studied this, including biochemical assays and mass spectrometry analyses. The study reveals that the NS5 protein of tick-borne encephalitis virus (TBEV) and Louping Ill virus (LIV), two related tick-borne flaviviruses, interact with the tyrosine kinase 2 (TYK2) to suppress JAK-STAT signaling. This interaction involves a specific sequence of 10 residues in the RNA dependent RNA polymerase domain of TBEV and LIV NS5. The study also shows that this interaction is conserved across mammalian species and reduces the catalytic activity of TYK2.
Gracias, Ségolène, et al. "Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2." EMBO reports (2023): e57424.
Pubmed: 37860832   DOI: 10.15252/embr.202357424