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

  • October 20-23, 2025

  • 9-1, Okazaki Seishojicho, Sakyo-ku Kyoto-shi, Kyoto, JP

Drug Metabolism and Pharmacokinetics (DMPK) plays a vital role in determining drug efficacy and safety, bridging fundamental research and clinical application. Recent years have seen remarkable advancements in DMPK technologies, driven by interdisciplinary insights and pioneering innovations. The growing diversity in drug discovery modalities also highlights the importance of further breakthroughs in pharmacokinetic research to meet emerging challenges.

The theme for this year’s meeting, "A Crossroad of Innovation, Shaping the Future of Drug Discovery and Pharmacotherapy," reflects Kyoto's unique role as a city where tradition and cutting-edge ideas intersect. This meeting aims to provide a valuable platform for researchers from various fields to exchange insights, collaborate, and explore new scientific approaches in pharmacokinetic research.

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    • Establish a High-Throughput Exposed Polar Surface Area (EPSA) Screening Platform

      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.

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    • Optimization and Assessment of Intrathecal (IT) Administration to Improve Drug Delivery to the CNS in Rats

      As a key protective mechanism of the central nervous system (CNS), the blood-brain barrier (BBB) effectively prevents the invasion of neurotoxic substances and blood-borne pathogens through selective permeability. However, this physiological characteristic also significantly limits the bioavailability of therapeutic drugs in the CNS when administered systemically, posing a major challenge in treating neurological diseases. Our team established novel dosing strategies via intrathecal (IT) catheterization in a rat model to enhance drug delivery to the CNS while significantly reducing physiological interference.

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    • Rapid Screening and Characterization of Payload-related Species Derived from ADCs in In Vitro Models by High-resolution Mass Spectrometry

      Understanding and characterizing the major released payload-related species is crucial for supporting lead optimization, bioanalytical method development, and ADME and DDI studies of ADCs.The objective of this study was to establish a quadrupole-orbitrap HRMS-based workflow for rapid screening and characterizing the payload-related species released from ADC after incubating with in vitro plasma, S9 fraction, lysosome, and tumor cells.

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    • A Novel and Accurate Method for Assessing the Stability of Maleimide-containing Linker-payloads in the β-glucuronidase Stability Assay

      In the development of ADC/PDC drugs, linker design and optimization are crucial. The stability of the linker-payload needs to be independently assessed within various in vitro biological incubation systems(e.g., plasma, lysosomes, cathepsin B, β-glucuronidase) without coupling to an antibody or peptide at the early screening stage. Maleimide is widely used as a linker for the conjugation of antibodies or peptides due to its rapid reactivity with thiol groups (-SH) under mild conditions. However, challenges emerge when assessing the stability of linker-payloads containing maleimide groups in in vitro biological matrices.

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    • Establishment of an In Vitro Screening System for Human Pregnane X Receptor (PXR) Agonists

      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.

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    • In Vitro Platform for Assessing ADC Stability and Payload Release

      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.

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