Tyk2-IN-13

Tyk2-IN-13 (compound 30) is an orally active TYK2 inhibitor. Tyk2-IN-13 inhibits IFNα stimulated STAT3 phosphorylation with an IC50 value of 1.90 nM. Tyk2-IN-13 can be used for the research of autoimmune diseases[1].

Signaling Pathways >> Immunology/Inflammation >> Interleukin Related

Research Areas >> Inflammation/Immunology

IL-6:33 nM (IC50)

IL-2:41 nM (IC50)

Tyk2-IN-13 (0-10 μM; 1.5 h) shows inhibitory effect to IFNα stimulated STAT3 phosphorylation with an IC50 value of 1.90 nM[1]. Tyk2-IN-13 (0.244-1000 nM; 30 min) exhibits binding affinities with IC50s of 3496, 41 and 33 nM for EPO, 1L-2 and 1L-6, respectively[1].

Tyk2-IN-13 (30 mg/kg; p.o. BID for 6 days) decreases the colonic weight of colitis mice[1]. Tyk2-IN-13 (20 mg/kg; p.o. BID for 5 days) weakens IL-23-induced acanthosis in vivo[1]. Animal Model: Male CB17-SCID mice with IL-23-dependent colitis[1] Dosage: 30 mg/kg Administration: Oral gavage; 30 mg/kg; twice daily for 6 days Result: Showed a decreasing effect in colonic weight, and no significant difference was observed relative to deucravacitinib. Animal Model: Female C57BL/6 mice with psoriasis-like skin inflammation[1] Dosage: 20 mg/kg Administration: Oral gavage; 20 mg/kg; twice daily for 5 days Result: Significantly protected mice from IL-23-induced acanthosis with no significant weight losses, and showed comparable results with deucravacitinib.

[1]. Liu Fei, et al. Novel TYK2 Inhibitors with an N-(Methyl-d3)pyridazine-3-carboxamide Skeleton for the Treatment of Autoimmune Diseases. ACS Medicinal Chemistry Letters. 2022.