| Identification | Back Directory | [Name]
Tyk2-IN-5 | [CAS]
1797432-62-2 | [Synonyms]
Tyk2-IN-5
Tyk2 inhibitor 5
Tyk2 IN 5,Tyk-2-IN-5,Tyk2IN5
Imidazo[1,2-b]pyridazine-3-carboxamide, N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)-6-[(2-oxo[1(2H),2'-bipyridin]-3-yl)amino]- | [Molecular Formula]
C21H19FN8O2 | [MOL File]
1797432-62-2.mol | [Molecular Weight]
434.43 |
| Chemical Properties | Back Directory | [density ]
1.58±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 43.33 mg/mL (99.74 mM; Need ultrasonic) | [form ]
Solid | [pka]
10.17±0.40(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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]. | Animal Model: | Lewis male rats (rat adjuvant arthritis model)[1]. | | 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)[1]. | | 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[1]. | | Dosage: | 10 mg/kg | | Administration: | Oral administration; single | | Result: | 1.19Pharmacokinetic Parameters of Tyk2-IN-5 in mouse and rat[1].
| PO (10 mg/kg) | | mouse | rat | | Cmax (μM) | 15 | 9.4 | | AUC0-24 (μM?h) | 19 | 57 | | CL (mL/min/kg) | 16 | 7.8 | | F (%) | 86 | 114 |
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| [IC 50]
Tyk2 JH2: 0.086 nM (Ki); IFNα: 25 nM (IC50) | [storage]
Store at -20°C | [References]
[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. DOI:10.1021/acsmedchemlett.9b00035 |
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