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NIK SMI1

CAS No. : 1660114-31-7

MCE 站：NIK SMI1

产品活性：NIK SMI1 是一种有效的选择性 NF-κB 诱导激酶 (NIK) 抑制剂，可抑制 NIK 催化的 ATP 水解为 ADP，IC₅₀ 为 0.23±0.17 nM。

研究领域：NF-κB

作用靶点：NF-κB

In Vitro: NIK SMI1 (Compound 4f) inhibits NIK-catalyzed hydrolysis of ATP to ADP (fluorescence polarization, FP) with an IC₅₀ of 0.23±0.17 nM. NIK SMI1 inhibits the expression of NIK SMI1 response elementregulated firefly luciferase reporter gene in HEK293 cells with an IC₅₀ of 34±6 nM. Consistent with expectations for a NIK inhibitor, NIK SMI1 is shown to inhibit nuclear translocation of p52 (RelB) (IC₅₀=70 nM). NIK SMI1 inhibits BAFF-induced B cell (mouse) survival in vitro with an IC₅₀ of 373±64 nM.

In Vivo: C57BL/6 mice are treated twice daily for 7 days with orally administered NIK SMI1 or with three injections of recombinant BAFF receptor fusion protein (Br3- mIgG2a) over the course of the 7-day experiment as a positive control. The nonlinearity of exposure relative to dose between 100 and 200 mg/kg is a result of saturation of clearance mechanisms. The pharmacology of NIK SMI1 is examined in SD rat, CD-1 mouse, beagle, and cynomologous monkey with 20, 32, 18, and 7.8 mL/kg per min, respectively. Volume of distribution (Vd, L/kg) is 1.35, 1.58, 0.778, and 1.39, respectively.

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