| Identification | Back Directory | [Name]
1H-Pyrazole-1-propanenitrile, 4-[5-fluoro-2-[[1-[(trifluoromethyl)sulfonyl]-1H-indol-5-yl]amino]-4-pyrimidinyl]- | [CAS]
2613434-12-9 | [Synonyms]
JAK2/TYK2-IN-1
1H-Pyrazole-1-propanenitrile, 4-[5-fluoro-2-[[1-[(trifluoromethyl)sulfonyl]-1H-indol-5-yl]amino]-4-pyrimidinyl]- | [Molecular Formula]
C19H13F4N7O2S | [MOL File]
2613434-12-9.mol | [Molecular Weight]
479.41 |
| Hazard Information | Back Directory | [Uses]
JAK2/TYK2-IN-2 is a potent and selective TYK2 inhibitor with IC50 values of 9 and 157 nM for TYK2 and JAK2, respectively. JAK2/TYK2-IN-2 has anti-inflammatory activity[1]. | [in vivo]
JAK2/TYK2-IN-2 (10 and 20 mg/kg; oral administration; twice a day for 6 consecutive days) exhibits anti-inflammatory activity in a dose-dependent manner[1].
JAK2/TYK2-IN-2 (5, 20 mg/kg; oral administration; twice a day for 12 days) leads to a low oral bioavailability[1].Pharmacokinetic Parameters of JAK1/TYK2-IN-2 in Male Sprague-Dawley rats[1]
| PK parameters | iv | PK parameters | p.o. | | AUC(0-t) (μg/L*h) | 29.00 | AUC(0-t) (μg/L*h) | 13.89 | | MRT(0-t) (h) | 4.98 | MRT(0-t) (h) | 2.76 | | t1/2 (h) | 5.95 | t1/2 (h) | 3.64 | | Cl (L/min/kg) | 1.58 | Cl (L/min/kg) | 20.55 | | Vss (L/kg) | 985.41 | Vss (L/kg) | 6564.28 | | Cmax (μg/L) | 48.55 | Cmax (μg/L) | 8.00 | | | Tmax (h) | 1.00 | | | F | 11.96% |
| Animal Model: | Six-eight week old male C57BL/6 mice, 20-22 g (acute mice colitis model)[1] | | Dosage: | 10, 20 mg/kg (dissolved in 5% EtOH, 1% Propylene glycol, 0.5% Tween 80 and 92.5% physiological saline) | | Administration: | Oral administration, twice a day; 6 consecutive days | | Result: | Exhibited anti-inflammatory activity and have a good therapeutic effect on inflammatory bowel disease (IBD) in a dose-dependent manner. |
| [IC 50]
Tyk2: 9 nM (IC50); JAK2: 157 nM (IC50) | [References]
[1] Zhang C, et al. Discovery of 3-(4-(2-((1H-Indol-5-yl) amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl) propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease. J Med Chem. 2021; 64(4):1966-1988. DOI:10.1021/acs.jmedchem.0c01468 |
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