《Discovery of a Potent and Selective NF-κB-Inducing Kinase (NIK) Inhibitor That Has Anti-inflammatory Effects in Vitro and in Vivo》 was written by 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. Safety of 2-(5-Methylisoxazol-3-yl)but-3-yn-2-ol And the article was included in Journal of Medicinal Chemistry on April 23 ,2020. The article conveys some information:
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. In addition to this study using 2-(5-Methylisoxazol-3-yl)but-3-yn-2-ol, there are many other studies that have used 2-(5-Methylisoxazol-3-yl)but-3-yn-2-ol(cas: 1202769-66-1Safety of 2-(5-Methylisoxazol-3-yl)but-3-yn-2-ol) was used in this study.
2-(5-Methylisoxazol-3-yl)but-3-yn-2-ol(cas: 1202769-66-1) belongs to isoxazoles. Isoxazoles is an oxygen-containing azole derivative found in some natural products such as amantine, as well as in several drugs, including COX-2 inhibitors and furoxan oxide (a nitric oxide donor). body). Safety of 2-(5-Methylisoxazol-3-yl)but-3-yn-2-olIsoxazoles are potent isosteres of pyridine and have been found to inhibit voltage-gated sodium channels for pain control, for the construction of tetracycline antibiotic derivatives, and as a therapeutic agent for depression.
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem