Evaluation of stabilizing additives to protect activities of cytochrome P450 enzymes for in vitro drug testing and pharmacogenetic studies: Focus on CYP2D6

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 4; p. 130770
• Main Authors: Yamoune, Sabrina, Koch, Henner, Delev, Daniel, Weber, Yvonne, Stingl, Julia Carolin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2025
• Subjects: Biocatalysis engineering; brain; Brain - enzymology; Brain - metabolism; Brain drug metabolism; CYP in vitro stability; CYP2D6; cysteine; cytochrome P-450; Cytochrome P-450 CYP2D6 - chemistry; Cytochrome P-450 CYP2D6 - metabolism; Cytochrome P-450 Enzyme System - metabolism; dithiothreitol; Dithiothreitol - chemistry; Dithiothreitol - pharmacology; drug development; drugs; Enzyme Stability - drug effects; enzymes; Humans; liver; liver microsomes; Local drug metabolism; Microsomes, Liver - enzymology; Microsomes, Liver - metabolism; organoids; Pharmacogenomic Testing - methods; pharmacokinetics; phosphorylcholine; safety assessment; Brain drug metabolism; DTT; DMSO; SOD; EtOH; Biocatalysis engineering; EDTA; MS/MS; AUC; BSA; CYP in vitro stability; PC; CYP2D6; MeOH; PMSF; Local drug metabolism; ROS; CYP; DLPC; KPB; Cys; GSH; HPLC

In vitro and ex vivo studies on drug metabolism and stability are vital for drug development and pre-clinical safety assessment. Traditional in vitro models, such as liver enzyme (S9) fractions and microsomes, often fail to account for individual variability. Personalized models, including 3D cell m...