Diterpenoid Vinigrol specifically activates ATF4/DDIT3-mediated PERK arm of unfolded protein response to drive non-apoptotic death of breast cancer cells was written by Wei, Wencheng;Li, Yunfei;Wang, Chuanxi;Gao, Sanxing;Zhao, Yan;Yang, Zhenyu;Wang, Hao;Gao, Ziying;Jiang, Yanxiang;He, Yuan;Zhao, Li;Gao, Hao;Yao, Xinsheng;Hu, Yuhui. And the article was included in Pharmacological Research in 2022.HPLC of Formula: 50-52-2 This article mentions the following:
Vinigrol is a natural diterpenoid with unprecedented chem. structure, driving great efforts into its total synthesis in the past decades. Despite anti-hypertension and anti-clot ever reported, comprehensive investigations on bioactions and mol. mechanisms of Vinigrol are entirely missing. Here we firstly carried out a complete functional prediction of Vinigrol using a transcriptome-based strategy coupled with multiple bioinformatic analyses and identified “anti-cancer” as the most prominent biofunction ahead of anti-hypertension and anti-depression/psychosis. Broad cytotoxicity was subsequently confirmed on multiple cancer types. Further mechanistic investigation on several breast cancer cells revealed that its anti-cancer effect was mainly through activating PERK/eIF2伪 arm of unfolded protein response (UPR) and subsequent non-apoptotic cell death independent of caspase activities. The other two branches of UPR, IRE1伪 and ATF6, were functionally irrelevant to Vinigrol-induced cell death. Using CRISPR/Cas9-based gene activation, repression, and knockout systems, we identified the essential contribution of ATF4 and DDIT3, not ATF6, to the death process. This study unraveled a broad anti-cancer function of Vinigrol and its underlying targets and regulatory mechanisms. It paved the way for further inspection on the structure-efficacy relationship of the whole compound family, making them a novel cluster of PERK-specific stress activators for exptl. and clin. uses. In the experiment, the researchers used many compounds, for example, 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2HPLC of Formula: 50-52-2).
10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.HPLC of Formula: 50-52-2
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem