Tyk2-IN-5 (C09-1183-489)

Tyk2-IN-5 (compound 6) is a potent, selective and orally active tyrosine kinase 2 ( Tyk2 ) inhibitor that acts on the JH2 structural domain. Tyk2-IN-5 shows a K i value of 0.086 nM for Tyk2 JH2 and an IC 50 value of 25 nM for IFNα. Tyk2-IN-5 efficiently inhibits the production of IFNγ in a pharmacodynamic rat model and is fully efficacious in a rat model of arthritisIn VitroTyk2-IN-5 inhibits Jak1-3 with IC 50 values of >2 μM and displays the Jak1-3 dependent cellular activities of >12.5 μM (IC 50 values). MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoTyk2-IN-5 (5, 10 mg/kg; p.o.; twice daily for 20 days) shows highly efficacious in a rat adjuvant arthritis model . Tyk2-IN-5 (1, 10 mg/kg; p.o.; single) inhibits IL-12/IL-18 induced IFNγ production in a dose-dependent manner . Tyk2-IN-5 (10 mg/kg; p.o.; single) shows a high oral exposure and bioavailability (114%) in rat . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Lewis male rats (rat adjuvant arthritis model) . Dosage: 5, 10 mg/kg Administration: Oral administration; twice daily for 20 days Result: Demonstrated full efficacy to prevent the rats′ paw from swelling. Animal Model: Lewis male rats (IL-12/IL-18-induced) . Dosage: 1, 10 mg/kg Administration: Oral administration; single Result: Inhibited IL-12/IL-18 induced IFNγ production by 45% and 77% at doses of 1 and 10 mg/kg, respectively. Animal Model: Lewis male rats, mouse . Dosage: 10 mg/kg Administration: Oral administration; single Result: 1.19 Pharmacokinetic Parameters of Tyk2-IN-5 in mouse and rat . PO (10 mg/kg) mouse rat C max (μM) 15 9.4 AUC 0-24 (μM•h) 19 57 CL (mL/min/kg) 16 7.8 F (%) 86 114IC50& Target:Tyk2 JH2 0.086 nM (Ki) IFNα 25 nM (IC 50 ). Specification: 10mM in DMSO Molecular Formula: C21H19FN8O2 Molecular Weight: 434.43