A podocyte-based automated screening assay identifies protective small molecules was written by Lee, Ha Won;Khan, Samia Q.;Faridi, Mohd. Hafeez;Wei, Changli;Tardi, Nicholas J.;Altintas, Mehmet M.;Elshabrawy, Hatem A.;Mangos, Steve;Quick, Kevin L.;Sever, Sanja;Reiser, Jochen;Gupta, Vineet. And the article was included in Journal of the American Society of Nephrology in 2015.Reference of 1226056-71-8 This article mentions the following:
Podocyte injury and loss mark an early step in the pathogenesis of various glomerular diseases, making these cells excellent targets for therapeutics. However, cell-based high-throughput screening assays for the rational development of podocyte-directed therapeutics are currently lacking. Here, we describe a novel high-content screening-based phenotypic assay that analyzes thousands of podocytes per assay condition in 96-well plates to quant. measure dose-dependent changes in multiple cellular features. Our assay consistently produced a Z’ value >0.44, making it suitable for compound screening. On screening with >2100 pharmacol. active agents, we identified 24 small mols. that protected podocytes against injury in vitro (1% hit rate). Among the identified hits, we confirmed an 尾1-integrin agonist, pyrintegrin, as a podocyte-protective agent. Treatment with pyrintegrin prevented damage-induced decreases in F-actin stress fibers, focal adhesions, and active 尾1-integrin levels in cultured cells. In vivo, administration of pyrintegrin protected mice from LPS-induced podocyte foot process effacement and proteinuria. Anal. of the murine glomeruli showed that LPS administration reduced the levels of active 尾1 integrin in the podocytes, which was prevented by cotreatment with pyrintegrin. In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside-induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic candidate and show the use of podocyte-based screening assays for identifying novel therapeutics for proteinuric kidney diseases. In the experiment, the researchers used many compounds, for example, N-Benzyl-2-(pyrimidin-4-ylamino)thiazole-4-carboxamide (cas: 1226056-71-8Reference of 1226056-71-8).
N-Benzyl-2-(pyrimidin-4-ylamino)thiazole-4-carboxamide (cas: 1226056-71-8) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.Reference of 1226056-71-8
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica