Characterization of a Structural Leoligin Analog as Farnesoid X Receptor Agonist and Modulator of Cholesterol Transport was written by Ladurner, Angela;Linder, Thomas;Wang, Limei;Hiebl, Verena;Schuster, Daniela;Schnuerch, Michael;Mihovilovic, Marko D.;Atanasov, Atanas G.;Dirsch, Verena M.. And the article was included in Planta Medica in 2020.Application of 5460-32-2 This article mentions the following:
The ligand-activated farnesoid X receptor is an emerging therapeutic target for the development of drugs against metabolic syndrome-related diseases. In this context, selective bile acid receptor modulators represent a novel concept for drug development. Selective bile acid receptor modulators act in a target gene- or tissue-specific way and are therefore considered less likely to elicit unwanted side effects. Based on leoligin, a lignan-type secondary plant metabolite from the alpine plant Leontopodium nivalessp. alpinum, 168 synthesized structural analogs were screened in a farnesoid X receptor in silicopharmacophore-model. Fifty-six virtual hits were generated. These hits were tested in a cell-based farnesoid X receptor transactivation assay and yielded 7 farnesoid X receptor-activating compounds The most active one being LT-141A, with an EC 50of 6μM and an E maxof 4.1-fold. This analog did not activate the G protein-coupled bile acid receptor, TGR5, and the metabolic nuclear receptors retinoid X receptor α, liver X receptors α/ β, and peroxisome proliferator-activated receptors β/ γ. Investigation of different farnesoid X receptor target genes characterized LT-141A as selective bile acid receptor modulators. Functional studies revealed that LT-141A increased cholesterol efflux from THP-1-derived macrophages viaenhanced ATP-binding cassette transporter 1 expression. Moreover, cholesterol uptake in differentiated Caco-2 cells was significantly decreased upon LT-141A treatment. In conclusion, the leoligin analog LT-141A selectively activates the nuclear receptor farnesoid X receptor and has an influence on cholesterol transport in 2 model systems. In the experiment, the researchers used many compounds, for example, 4-Iodo-1,2-dimethoxybenzene (cas: 5460-32-2Application of 5460-32-2).
4-Iodo-1,2-dimethoxybenzene (cas: 5460-32-2) belongs to iodide derivatives. Organic iodides are widely used in organic synthesis. Halogenation of aromatic hydrocarbons is a very important reaction via an electrophilic aromatic substitution. In the chemical industry, alkyl iodides serve as excellent alkylating agents and, specifically, methyl iodide is used as a methylating agent in the synthesis of various pharmaceutical drugs.Application of 5460-32-2
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com