Small-Molecule TLR8 Antagonists via Structure-Based Rational Design was written by Hu, Zhenyi;Tanji, Hiromi;Jiang, Shuangshuang;Zhang, Shuting;Koo, Kyoin;Chan, Jean;Sakaniwa, Kentaro;Ohto, Umeharu;Candia, Albert;Shimizu, Toshiyuki;Yin, Hang. And the article was included in Cell Chemical Biology in 2018.Application of 525362-07-6 This article mentions the following:
Rational design of drug-like small-mol. ligands based on structural information of proteins remains a significant challenge in chem. biol. In particular, designs targeting protein-protein interfaces have met little success given the dynamic nature of the protein surfaces. Herein, we utilized the structure of a small-mol. ligand in complex with Toll-like receptor 8 (TLR8) as a model system due to TLR8′s clin. relevance. Overactivation of TLR8 has been suggested to play a prominent role in the pathogenesis of various autoimmune diseases; however, there are still few small-mol. antagonists available, and our rational designs led to the discovery of six exceptionally potent compounds with ~picomolar IC50 values. Two X-ray crystallog. structures validated the contacts within the binding pocket. A variety of biol. evaluations in cultured cell lines, human peripheral blood mononuclear cells, and splenocytes from human TLR8-transgenic mice further demonstrated these TLR8 inhibitors′ high efficacy, suggesting strong therapeutic potential against autoimmune disorders. In the experiment, the researchers used many compounds, for example, Methyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (cas: 525362-07-6Application of 525362-07-6).
Methyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (cas: 525362-07-6) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Application of 525362-07-6
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics