Tyk2-IN-5

• CAT Number: I019405
• CAS Number: 1797432-62-2
• Molecular Formula: C21H19FN8O2
• Molecular Weight: 434.43
• Purity: ≥95%
• Synonyms: N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)-6-[(2-oxo-1-pyridin-2-ylpyridin-3-yl)amino]imidazo[1,2-b]pyridazine-3-carboxamide
• InChI: InChI=1S/C21H19FN8O2/c1-23-15-10-17(26-13-5-4-8-29(21(13)32)18-6-2-3-7-24-18)28-30-16(11-25-19(15)30)20(31)27-14-9-12(14)22/h2-8,10-12,14,23H,9H2,1H3,(H,26,28)(H,27,31)/t12-,14+/m0/s1
• InChIKey: YITUGUNLCGLOII-GXTWGEPZSA-N
• SMILES: CNC1=CC(=NN2C1=NC=C2C(=O)NC3CC3F)NC4=CC=CN(C4=O)C5=CC=CC=N5

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 Ki value of 0.086 nM for Tyk2 JH2 and an IC50 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 arthritis[1].
Tyk2-IN-5 inhibits Jak1-3 with IC50 values of >2 μM and displays the Jak1-3 dependent cellular activities of >12.5 μM (IC50 values)[1].
Tyk2-IN-5 (5, 10 mg/kg; p.o.; twice daily for 20 days) shows highly efficacious in a rat adjuvant arthritis model[1].
Tyk2-IN-5 (1, 10 mg/kg; p.o.; single) inhibits IL-12/IL-18 induced IFNγ production in a dose-dependent manner[1].
Tyk2-IN-5 (10 mg/kg; p.o.; single) shows a high oral exposure and bioavailability (114%) in rat[1].

Reference

[1]. Liu C, et al. Identification of Imidazo[1,2-b]pyridazine Derivatives as Potent, Selective, and Orally Active Tyk2 JH2 Inhibitors. ACS Med Chem Lett. 2019 Feb 21;10(3):383-388.
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