Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage was written by Wang, Di;Li, Danting;Zhang, Yuxin;Chen, Jie;Zhang, Ying;Liao, Chuyao;Qin, Siyuan;Tian, Yuan;Zhang, Zunjian;Xu, Fengguo. And the article was included in Acta Pharmaceutica Sinica B in 2021.Category: piperazines This article mentions the following:
Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) pos. feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) neg. feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, resp. Moreover, based on virtual screening and biol. verification, vardenafil and linagliptin as GPR35 and AHR agonists resp. were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity in vivo suggests that chemotherapeutics combined with the two could be a promising therapeutic strategy for cancer patients in clinic. This work highlights GPR35 and AHR as the guardian of kynurenine pathway metabolism and core component of defense responses against intestinal damage. In the experiment, the researchers used many compounds, for example, 2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (cas: 224785-90-4Category: piperazines).
2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (cas: 224785-90-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Category: piperazines
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics