100516-88-9Relevant articles and documents
Design, synthesis, and LFA-1/ICAM-1 antagonist activity evaluation of Lifitegrast analogues
An, Yuanlong,Du, Guoxin,Du, Weiwei,Gong, Qi,Hao, Feifei,He, Wei,He, Xiangdong,Jiang, Hualiang,Tong, Xiaochu,Wang, Minnan,Zhang, Donglei,Zheng, Mingyue
, (2022/02/22)
The interaction between Lymphocyte function-associated antigen 1 (LFA-1) and intercellular-adhesion molecule-1 (ICAM-1) plays important roles in the cell-mediated immune response and inflammation associated with dry eye disease. LFA-1/ICAM-1 antagonists can be used for the treatment of dry eye disease, such as Lifitegrast which has been approved by the FDA in 2016 as a new drug for the treatment of dry eye disease. In this study, we designed and synthesized some new structure compounds that are analogues to Lifitegrast, and their biological activities were evaluated by in vitro cell-based assay and also by in vivo mouse dry eye model. Our results demonstrated that one of these analogues of Lifitegrast (compound 1b) showed good LFA-1/ICAM-1 antagonist activity in in vitro assay; meanwhile, it also significantly reduced ocular surface epithelial cells damage, increased goblet cell density in dry eye mouse and highly improved the symptoms of dry eye mouse. [Figure not available: see fulltext.]
Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery
Solbak, Sara Marie ?ie,Zang, Jie,Narayanan, Dilip,H?j, Lars Jakobsen,Bucciarelli, Saskia,Softley, Charlotte,Meier, Sebastian,Langkilde, Annette Eva,Gotfredsen, Charlotte Held,Sattler, Michael,Bach, Anders
, p. 1156 - 1177 (2020/03/10)
Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phoxSH3A-B) with KD values of 400-600 μM. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phoxSH3A-B and these competed with p22phox for binding to p47phoxSH3A-B. Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phoxSH3A-B-p22phox interaction (Ki of 20 μM). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.
Unique nanocages of 12CaO·7Al2O3 boost heterolytic hydrogen activation and selective hydrogenation of heteroarenes over ruthenium catalyst
Ye, Tian-Nan,Li, Jiang,Kitano, Masaaki,Hosono, Hideo
, p. 749 - 756 (2017/05/22)
The chemoselective hydrogenation of heteroarenes is one of the most important synthetic reactions for the production of key intermediates in agrochemicals, pharmaceuticals and various fine chemicals. The development of new heterogeneous catalysts for the environmentally benign synthesis of heterocycle hydrogenated products is a fundamental objective for chemists. Here, we report that 12CaO·7Al2O3 with a unique sub-nanocage structure loaded with Ru nanoparticles exhibits higher activity, chemoselectivity and sustainability for the hydrogenation of heteroarenes in a solvent-free system than traditional oxide-supported metal catalysts. Conversion of >99% and a selectivity close to 99% were achieved for the hydrogenation of quinoline under mild conditions. This catalyst was also successfully applied to the hydrogenation of a variety of N- and O-heteroarenes with high yields. The superior catalytic performance can be attributed to a cooperative effect between the hydrogen-storage ability and large amount of strong basic sites on the surface of the support, which promotes heterolytic H2 cleavage and prevents poisoning of the metal surface caused by the adsorption of heteroarenes.
