Usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells for the prediction of intestinal drug absorption in humans was written by Michiba, Kazuyoshi;Maeda, Kazuya;Shimomura, Osamu;Miyazaki, Yoshihiro;Hashimoto, Shinji;Oda, Tatsuya;Kusuhara, Hiroyuki. And the article was included in Drug Metabolism & Disposition in 2022.Quality Control of 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid The following contents are mentioned in the article:
This study aimed to demonstrate the usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells as a novel in vitro model for clarifying the impact of intestinal drug-metabolizing enzymes and transporters on the intestinal absorption of substrate drugs in humans. Three-dimensional human intestinal spheroids were successfully established from surgical human jejunal specimens and expanded for a long period using L-WRN-conditioned medium, which contains Wnt3a, R-spondin 3, and noggin. The mRNA expression levels of intestinal pharmacokinetics-related genes in the human jejunal spheroid-derived differentiated intestinal epithelial cells were drastically increased over a 5-day period after seeding compared with those in human jejunal spheroids and were approx. the same as those in human jejunal tissue over a culture period of at least 13 days. Activities of typical drug-metabolizing enzymes [cytochrome P 450 (CYP) 3A, CYP2C9, uridine 5-diphospho-glucuronosyltransferase 1A, and carboxylesterase 2] and uptake/efflux transporters [peptide transporter 1/solute carrier 15A1], P-glycoprotein, and breast cancer resistance protein) in the differentiated cells were confirmed. Furthermore, intestinal availability (Fg) values estimated from the apical-to-basolateral permeation clearance across cell monolayer showed a good correlation with the in vivo Fg values in humans for five CYP3A substrate drugs (Fg range, 0.35-0.98). In conclusion, the functions of major intestinal drug-metabolizing enzymes and transporters could be maintained in human jejunal spheroid-derived differentiated intestinal epithelial cells. This model would be useful for the quant. evaluation of the impact of intestinal drug-metabolizing enzymes and transporters on the intestinal absorption of substrate drugs in humans. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Quality Control of 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid).
2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Quality Control of 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem