An article Triazole-Based Inhibitors of the Wnt/beta-Catenin Signaling Pathway Improve Glucose and Lipid Metabolisms in Diet-Induced Obese Mice WOS:000457067600022 published article about BETA-CATENIN; NEGATIVE REGULATOR; WNT; TCF7L2; GENE; ACTIVATION; BINDING; RISK; SUSCEPTIBILITY; MECHANISMS in [Obianom, Obinna N.; Ai, Yong; Li, Yingjun; Yang, Wei; Guo, Dong; Yang, Hong; Xue, Fengtian; Shu, Yan] Univ Maryland, Sch Pharm, Dept Pharmacal Sci, Baltimore, MD 21201 USA; [Sakamuru, Srilatha; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA; [Shu, Yan] Guangzhou Med Univ, Sch & Hosp Stomatol, Guangzhou 510140, Guangdong, Peoples R China; [Yang, Wei] Jiangsu Food & Pharmaceut Sci Coll, Pharmaceut Engn, Huaian 223005, Jiangsu, Peoples R China in 2019, Cited 51. Quality Control of 2-Aminobenzamide. The Name is 2-Aminobenzamide. Through research, I have a further understanding and discovery of 88-68-6
Wnt/beta-catenin signaling pathway is implicated in the etiology and progression of metabolic disorders. Although lines of genetic evidence suggest that blockage of this pathway yields favorable outcomes in treating such ailments, few inhibitors have been used to validate the promising genetic findings. Here, we synthesized and characterized a novel class of triazole-based Wnt/beta-catenin signaling inhibitors and assessed their effects on energy metabolism. One of the top inhibitors, compound 3a, promoted Axin stabilization, which led to the proteasome degradation of beta-catenin and subsequent inhibition of the Wnt/beta-catenin signaling in cells. Treatment of hepatocytes and high fat diet-fed mice with compound 3a resulted in significantly decreased hepatic lipid accumulation. Moreover, compound 3a improved glucose tolerance of high fat diet-fed mice without noticeable toxicity, while downregulating the genes involved in the glucose and fatty acid anabolisms. The new inhibitors are expected to be further developed for the treatment of metabolic disorders.
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