JAK1/TYK2-IN-3 是一种有效的，选择性和口服活性的双重TYK2/JAK1抑制剂，IC50值分别为 6 和 37 nM。JAK1/TYK2-IN-3 选择性的作用于JAK2(IC50=140 nM) 和JAK3(IC50=362 nM)。JAK1/TYK2-IN-3 通过调节TYK2/JAK1相关基因的表达以及 Th1 、Th2 和 Th17 细胞的形成来发挥抗炎作用。
| 生物活性 | JAK1/TYK2-IN-3 is a potent, selective and orally active dualTYK2/JAK1inhibitor withIC50values of 6 and 37 nM, respectively. JAK1/TYK2-IN-3 also shows selectively relative toJAK2(IC50=140 nM) andJAK3(IC50=362 nM). JAK1/TYK2-IN-3 shows anti-inflammatory effect by regulating the expression of relatedTYK2/JAK1-regulated genes, as well as the formation of Th1, Th2, and Th17 cells[1]. |
| IC50& Target | Tyk2 6 nM (IC50) | JAK1 37 nM (IC50) | JAK2 140 nM (IC50) | JAK3 362 nM (IC50) |
|
体外研究
(In Vitro) | JAK1/TYK2-IN-3 (compound 48) (10, 20, 30 mg/kg) shows anti-inflammatory effect by regulating the formation of Th1, Th2, Th17 cells[1].
JAK1/TYK2-IN-3 (10, 20, 30 mg/kg) inhibits the NF-κB signaling pathway by inhibits the JAK-STAT pathway, thereby reducing the inflammatory response in ulcerative colitis (UC) mice[1].
JAK1/TYK2-IN-3 (10, 20, 30 mg/kg) dose-dependently inhibits the mRNA expression of TNF-α, IL-1β, IL-12, IL-17A, IL-22, IFN-α, and IFN-β[1].
|
体内研究
(In Vivo) | JAK1/TYK2-IN-3 (10, 20, 30 mg/kg; p.o.; twice a day for 12 days) shows a good therapeutic effect on ulcerative colitis (UC)[1].
JAK1/TYK2-IN-3 (5 mg/kg, p.o.) shows 23.7% oral bioavailability in rats[1].
Pharmacokinetic Parameters of JAK1/TYK2-IN-3 in male Sprague-Dawley rats[1].
| compd | dose(mg/kg) | Administration | Cmax(ng/mL) | Cl (Lh-1kg-1) | T1/2(h) | AUC0-t(ng·h/mL) | F (%) | | 48 | 5 mg/kg | p.o. | 400.4±55.3 | 11.3±5.2 | 2.4±2.1 | 440.9±157.0 | 23.7 |
| Animal Model: | 6-8 weeks, 270-325g male Sprague-Dawley rats[1] | | Dosage: | 5 mg/kg | | Administration: | p.o. | | Result: | Showed 23.7% oral bioavailability in rats. |
| Animal Model: | Six-eight week old male C57BL/6 mice, 20-22 g (2.5% dextran sulfate sodium (DSS)-induced acute UC mouse model)[1] | | Dosage: | 10, 20, 30 mg/kg | | Administration: | p.o., twice a day, 12 days | | Result: | Improved the infiltration of inflammatory factors and reduced the damage caused by DSS. |
|
| 分子量 | |
| Formula | |
| CAS 号 | |
| 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. |
m.cnreagent.com