Cadefrecitinib (GLPG3667) is a reversible, ATP-competitive and orally active TYK2 inhibitor with an IC50 of 2.3 nM. Cadefrecitinib inhibits IFNα/pSTAT1, and the IC50 values in human peripheral blood mononuclear cell (PBMC) and whole blood assays are 70 nM and 623 nM, respectively. Cadefrecitinib has the potential for the study of inflammatory and autoimmune diseases [1].
In Vivo, Cadefrecitinib (GLPG3667) (3-30 mg/kg; oral administration, once daily (q.d.); for 5 days) reduces dermal ear inflammation in an IL-23-induced in vivo mouse model of psoriasis[1].
In Vitro, Cadefrecitinib (GLPG3667) shows dose-dependent inhibition of IFNα-induced STAT1 phosphorylation, demonstrating its selectivity and potency against TYK2 in relevant assays (PBMC and whole blood). In human peripheral blood mononuclear cells (PBMCs), the IC50 values for JAK1/TYK2, JAK1/JAK3, and JAK2 are 70 nM, 1113 nM, and 1022 nM, respectively. Its potency is notably higher in the TYK2-dependent pathway compared to JAK1 and JAK2 pathways, confirming its selective TYK2 inhibition profile[1].
References:
[1]. Mammoliti O, et al. Discovery of GLPG3667, a Selective ATP Competitive Tyrosine Kinase 2 Inhibitor for the Treatment of Autoimmune Diseases. J Med Chem. 2024 Jun 13;67(11):8545-8568.
In Vivo, Cadefrecitinib (GLPG3667) (3-30 mg/kg; oral administration, once daily (q.d.); for 5 days) reduces dermal ear inflammation in an IL-23-induced in vivo mouse model of psoriasis[1].
In Vitro, Cadefrecitinib (GLPG3667) shows dose-dependent inhibition of IFNα-induced STAT1 phosphorylation, demonstrating its selectivity and potency against TYK2 in relevant assays (PBMC and whole blood). In human peripheral blood mononuclear cells (PBMCs), the IC50 values for JAK1/TYK2, JAK1/JAK3, and JAK2 are 70 nM, 1113 nM, and 1022 nM, respectively. Its potency is notably higher in the TYK2-dependent pathway compared to JAK1 and JAK2 pathways, confirming its selective TYK2 inhibition profile[1].
References:
[1]. Mammoliti O, et al. Discovery of GLPG3667, a Selective ATP Competitive Tyrosine Kinase 2 Inhibitor for the Treatment of Autoimmune Diseases. J Med Chem. 2024 Jun 13;67(11):8545-8568.