Identification of Human Alanine-Glyoxylate Aminotransferase Ligands as Pharmacological Chaperones for Variants Associated with Primary Hyperoxaluria Type 1 was written by Grottelli, Silvia;Annunziato, Giannamaria;Pampalone, Gioena;Pieroni, Marco;Dindo, Mirco;Ferlenghi, Francesca;Costantino, Gabriele;Cellini, Barbara. And the article was included in Journal of Medicinal Chemistry in 2022.Application of 14425-64-0 This article mentions the following:
Primary hyperoxaluria type I (PH1) is a rare kidney disease due to the deficit of alanine:glyoxylate aminotransferase (AGT), a pyridoxal-5′-phosphate-dependent enzyme responsible for liver glyoxylate detoxification, which in turn prevents oxalate formation and precipitation as kidney stones. Many PH1-associated missense mutations cause AGT misfolding. Therefore, the use of pharmacol. chaperones (PCs), small mols. that promote correct folding, represents a useful therapeutic option. To identify ligands acting as PCs for AGT, we first performed a small screening of com. available compounds We tested each mol. by a dual approach aimed at defining the inhibition potency on purified proteins and the chaperone activity in cells expressing a misfolded variant associated with PH1. We then performed a chem. optimization campaign and tested the resulting synthetic mols. using the same approach. Overall, the results allowed us to identify a promising hit compound for AGT and draw conclusions about the requirements for optimal PC activity. In the experiment, the researchers used many compounds, for example, 1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0Application of 14425-64-0).
1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.Application of 14425-64-0
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