Li, Zhiqiang; Li, Xinzhi; Su, Ming-Bo; Gao, Li-Xin; Zhou, Yu-Bo; Yuan, Bingchuan; Lyu, Xilin; Yan, Ziqin; Hu, Chujiao; Zhang, Hao; Luo, Cheng; Chen, Zheng; Li, Jia; Zhao, Yujun published the artcile< Discovery of a Potent and Selective NF-κB-Inducing Kinase (NIK) Inhibitor That Has Anti-inflammatory Effects in Vitro and in Vivo>, Category: pyrimidines, the main research area is preparation NFkappaB inducing kinase inhibitor antiinflammatory toxic hepatitis; pyrrolopyrimidine amino preparation antiinflammatory hepatitis.
The overexpression of NIK plays a critical role in liver inflammatory diseases. Treatment of such diseases with small-mol. NIK inhibitors is a reasonable but underexplored approach. In this paper, we reported the discovery of a potent and selective NIK inhibitor I (XT2). The compound I inhibited the NIK kinase with an IC50 value of 9.1 nM in vitro, and it also potently suppressed NIK activities in intact cells. In isogenic primary hepatocytes, treatment with I efficiently suppressed the expressions of NIK-induced genes. The compound I was orally bioavailable in mice with moderate systemic exposure. In a NIK-associated mouse liver inflammation model, the compound I suppressed CCl4-induced upregulation of ALT, a key biomarker of acute liver injury, and also decreased immune cell infiltration into the injured liver tissue. Overall, these studies provide examples that an NIK inhibitor is able to suppress toxin-induced liver inflammations, which indicates its therapeutic potentials for the treatment of liver inflammatory diseases.
Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Category: pyrimidines.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia