JAK2/TYK2-IN-1

JAK2/TYK2-IN-1;

JAK2/TYK2-IN-2 是一种有效的选择性 TYK2JAK2 抑制剂,IC50 值分别为 9 和 157 nM。JAK2/TYK2-IN-2 还具有抗炎活性。

JAK2/TYK2-IN-1amp;;

JAK2/TYK2-IN-1 Chemical Structure

CAS No. : 2613434-12-9

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生物活性

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].

IC50 Target

Tyk2

9 nM (IC50)

JAK2

157 nM (IC50)

体外研究
(In Vitro)

JAK2/TYK2-IN-2 (compound 14l; 0-10000 nM) inhibits the phosphorylation of STAT in vitro[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: TF-1, H9, TF-1, THP-1 cells
Concentration: 0-10000 nM
Incubation Time:
Result: After stimulation with IL-6 and IFN-α at a concentration of 100 to 5000 nM, JAK2/TYK2-IN-2 reduced JAK1/JAK2/TYK2 and JAK1/TYK2-dependent signal transduction in a dose-dependent manner and remarkably reduced IFN-α-induced phosphorylation at 10 000 nM.

体内研究
(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%

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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.

分子量

479.41

Formula

C19H13F4N7O2S

CAS 号

2613434-12-9

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.

参考文献
  • [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.

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