The 40th Annual Meeting of the Japanese Society for the Study of Xenobiotics

Exposed polar surface area (EPSA), which assays PSA experimentally, has emerged as a valuable tool to screen for potentially permeable “beyond rule of 5” (bRo5) compounds —promising candidates for developing treatments targeting previously undruggable sites. As bRo5 drugs play an increasingly crucial role in treating complex diseases but have poor oral pharmacokinetics, it is significantly important to establish a more rapid screening platform for potentially permeable drugs to provide essential guidance for molecular modification.

The present study aims to establish a HepG2 cell model that overexpresses the human PXR gene and CYP3A promoter, facilitating the rapid identification of PXR agonists during the early stages of the preclinical phase.

Antibody-drug conjugates (ADCs) exert cytotoxic effects through binding to cell surface antigens, internalization via endocytosis, and subsequent payload release within endosomal/lysosomal compartments. This study aimed to develop in vitro platforms for evaluating ADC payload release mechanisms, particularly enzyme-mediated linker cleavage.