| Identification | Back Directory | [Name]
5H-Pyrrolo[3,4-b]pyridin-5-one, 2-(2,6-difluorophenyl)-6,7-dihydro-4-[[4-(1-pyrrolidinylcarbonyl)phenyl]amino]- | [CAS]
2244061-66-1 | [Synonyms]
TYK2-IN-12
2-(2,6-Difluoro-phenyl)-4-[4-(pyrrolidine-1-carbonyl)-phenylamino]-6,7-dihydro-pyrrolo[3,4-b]pyridin-5-one
2-(2,6-Difluorophenyl)-4-((4-(pyrrolidine-1-carbonyl)phenyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one
5H-Pyrrolo[3,4-b]pyridin-5-one, 2-(2,6-difluorophenyl)-6,7-dihydro-4-[[4-(1-pyrrolidinylcarbonyl)phenyl]amino]- | [Molecular Formula]
C24H20F2N4O2 | [MOL File]
2244061-66-1.mol | [Molecular Weight]
434.44 |
| Chemical Properties | Back Directory | [Boiling point ]
682.8±55.0 °C(Predicted) | [density ]
1.395±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
4.22±0.20(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
TYK2-IN-12 (compound 30) is an orally active, potent and selective TYK2 (tyrosine kinase 2) inhibitor, with a Ki of 0.51 nM. TYK2-IN-12 inhibits IL-12 induced IFNγ, with IC50 values of 2.7 and 7.0 μM in human and mouse whole blood, respectively. TYK2-IN-12 can be used for psoriasis research[1]. | [in vivo]
TYK2-IN-12 (compound 30) (0-100 mg/kg, PO, daily for 10 days) dose-dependently reduces immune responses[1].
TYK2-IN-12 (3 mg/kg (IV), 10 mg/kg (PO), once) shows moderate clearance and volumes of distribution, and exhibits moderate to good oral absorption[1].
Pharmacokinetic Parameters of TYK2-IN-12 in male C57Bl/6 mice and smale Sprague-Dawley rats[1].
| Species | Mouse | Rat | | PPB Fumax (h) | 0.061 | 0.10 | | CL (mL/min/kg) | 28 | 27 | | t1/2 (h) | 1.8 | 1.6 | | Vd (L/kg) | 1.2 | 1.9 | | F (%) | >90 | 32 |
| Animal Model: | C57BL/6 mice (IL-23 induced inflammation model)[1] | | Dosage: | 0, 10, 30, and 100 mg/kg | | Administration: | PO, daily for 10 days | | Result: | Dose-dependently reduced immune responses, with up to 74 % inhibition of ear swelling and 96 % inhibition of tissue levels of IL-17A at 100 mg/kg, highlighting the crucial role of TYK2 in IL-23 induced IL-17 and tissue inflammation. Exhibited improved skin histology and a dose-dependent reduction of spleen weight. |
| Animal Model: | Male C57Bl/6 mice, male SD rats[1] | | Dosage: | 3 mg/kg (IV), 10 mg/kg (PO) | | Administration: | IV or PO, once (Pharmacokinetic Analysis) | | Result: | Showed moderate clearance and volumes of distribution of 1.2 L/Kg and 1.9 L/Kg, respectively in mouse and rat IV PK, and exhibited moderate to good oral absorption, with oral bioavailabilities of 32-100%. |
| [IC 50]
Tyk2: 0.51 nM (Ki); JAK3: 6.63 nM (Ki); JAK2: 21.93 nM (Ki); JAK1: 45.9 nM (Ki) | [References]
[1] Leit S, et al. Potent and selective TYK2-JH1 inhibitors highly efficacious in rodent model of psoriasis. Bioorg Med Chem Lett. 2022 Jul 13;73:128891. DOI:10.1016/j.bmcl.2022.128891 |
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