The 26th International Symposium on Microsomes and Drug Oxidations

This symposium, consisting of three leading investigators on this topic plus one selected abstract presenter, will cover the most recent advances in noncoding RNA-controlled regulation of drug metabolism and disposition. The speakers will present their own data to demonstrate 1) the involvement of microRNAs and lncRNAs in the control of ADME gene expression, 2) the underlying mechanisms, and 3) consequent impact on drug metabolism and disposition as well as drug efficacy and toxicity. Its contribution to improving the understanding of inter-individual variations in ADME/PK will be discussed. This symposium will be available for all MDO registrants who are expected to learn the fundamental principles in noncoding RNAs, posttranscriptional gene regulation, and other new regulatory mechanisms.

This symposium will focus on the most recent advances regarding the clinical importance of drug transporters. This session will bring together leading experts in the field to overview clinically relevant transporter issues and the speakers’ latest findings on the 1) roles of membrane transporters in drug/endobiotic transport/homeostasis, pharmacokinetics and drug efficacy and toxicity, and 2) the expression and regulation of transporters in the context of human diseases, with a focus on specific organs or populations. New strategies for targeting drug transporters to improve efficacy and minimize toxicity will be discussed. This symposium will be available for all MDO registrants who are expected to learn the fundamental principles and new strategies in drug transporters in drug development and clinical therapy.

For many years we have recognized that cytochrome P450 (P450, CYP) enzymes interact with their electron donors. In the case of mitochondrial P450s, it is adrenodoxin. With microsomal P450s, it is NADPH-P450 reductase (POR), and there are still some different conclusions about the role of cytochrome b5 (b5). Gaps in our knowledge still exist, and recently there have been some new developments in our appreciation of the organization of these proteins and with some other proteins.

Drug metabolism and pharmacokinetics (DMPK) studies for nucleic acid therapeutics are crucial for understanding how these novel drug modalities are absorbed, distributed, metabolized, and excreted in the body, as well as how they affect the therapeutic efficacy, adverse reactions, toxicity, and drug-drug interactions (DDIs). This knowledge is essential for optimizing drug delivery, dosage, and clinical trial design. The session includes three invited speakers from an academic university, a government institute, and a pharmaceutical company to discuss the advanced knowledge on DMPK, efficacy, and DDIs of ASOs, siRNAs, and lncRNA motifs. A short talk will be selected from a trainee who submits an abstract to the meeting.

Bile acids (BAs) are increasingly recognized as dynamic metabolic regulators that extend far beyond their traditional roles in lipid digestion and cholesterol homeostasis. As central integrators of hepatic, intestinal, and microbial metabolism, BAs modulate drug biotransformation, energy balance, glucose and lipid metabolism, and inflammatory responses. This session will focus on recent advances in bile acid metabolic pathways, including their enzymatic synthesis, microbial biotransformation, and regulation by nuclear and membrane receptors. Particular emphasis will be placed on the metabolic consequences of BA signaling in health and disease, especially in the context of metabolic dysfunction-associated liver diseases. Cutting-edge approaches—including metabolomics, transcriptomics, and integrated host-microbiome analyses—will be highlighted, along with translational insights into therapeutic targeting of bile acid metabolism. This session brings together global experts to foster interdisciplinary exchange at the interface of metabolism, pharmacology, and microbiome science.

Traditional medical systems are gaining increasing global recognition. Despite the widespread availability of modern pharmaceuticals, medicinal herbal products continue to be widely used, often rooted in longstanding historical and cultural practices. At the same time, interest in functional natural products—including medicinal herbs—is growing in Western countries. This session explores herbal medicines and functional natural products, focusing on the bioactive substances responsible for their therapeutic, health-promoting, or adverse effects. It also examines the roles of drug-metabolizing enzymes and transporters in the pharmacokinetics of these substances and their potential for drug interactions. Emphasizing an interdisciplinary perspective, the session aims to promote the effective and rational use of herbal medicines and functional natural products while highlighting strategies for risk mitigation.

Herbal medicines and functional natural products are gaining global attention for their therapeutic potential, especially in the context of integrative and personalized medicine. Despite their widespread use, the scientific understanding of their pharmacokinetics, interactions, and pharmacological mechanism profiles remains incomplete. This session will explore cutting-edge advances in the mechanistic evaluation of herbal constituents and functional compounds, with an emphasis on host cytochrome P450 (CYP) enzyme and microbiota co-mediated metabolism and its implications for drug efficacy and toxicity. By bringing together experts around the world, this session aims to foster a multidisciplinary dialogue on the innovative research of herbal medicines. Key topics include: major phytochemicals (e.g., polysaccharides, alkaloids) and their unique metabolism pathway; natural products and its interaction networks with host diseases; innovative tools and technologies for natural product metabolism researching. This session will help bridge traditional herbal medicines use with latest knowledge on drug metabolism, supporting safer and rational applications of natural products in contemporary healthcare

Cytochrome P450 enzymes are key catalytic proteins responsible for metabolizing majority of pharmaceutical agents. Inhibition/inactivation of these enzymes can take place due to co-intaking other medications, diets, and fruit and are considered as the major factor responsible for drug-drug interactions (DDIs). Such P450-mediated DDIs may increase the toxicities of therapeutic agents and decrease the efficacy of pro-drugs. The session will cover recent advances in 1) understanding of mechanisms involved in the action of P450 inhibitors/inactivators resulting in alterations of PKPD; 2) approaches to minimize P450-mediated DDIs in rational drug design; 3) extrapolation from in vitro to in vivo and from animals to humans; and 4) prediction of in vivo issues. The speakers come from North America, Europe, and Asia. They are two seniors and one junior (female). Two speakers represent academia, and one comes from industry.

Organ toxicity and variable therapeutic efficacy are two main challenges associated with current drug treatments. In order to optimize drug treatments, it is vital to understand the disposition of drugs and their metabolites in target tissues. When a drug interacts with tissues and cells, it could be affecting a wide range of endogenous biomolecules. Therefore, it is crucial to employ novel integrated technologies and approaches that provide information across multiple levels, including several classes of molecules to investigate the effects of drugs and their metabolites on endogenous molecules. This symposium brings together several leading investigators from academia and industry in related areas to present their most recent research on drug metabolism, disposition, and response research with novel high-resolution and cellular approaches. The attendees will have a better understanding of (1) spatially resolved multi-omics approaches, including high-resolution mass spectrometry imaging facilitating the interrogation of drug disposition and response at the cell- type level in both tissues and human organoids, (2) application of breast cancer cell models to investigate the effect of drugs on lipid metabolic pathways, and (3) hydrolase phenotyping and microbiome contribution to reduction metabolite formation. One short talk will be included from the submitted abstracts.

A brief description of the scientific background and the key contents to be presented (250-word limit): Drug-induced liver toxicity is a major clinical concern. The involved "drugs" range from natural products, medicinal herbs, prescription drugs, and over the counter medications. The Session will provide case studies to understand the chemical mechanisms to explain the toxicity, the host factors that dictate the sensitivity to drug-induced liver injury, as well as mechanism-based approaches to mitigate drug-induced liver injury. All speakers are investigators who are active in the topic field. The planned speakers include those from China and USA.

Pregnane X receptor (PXR) and Constitutive Androstane Receptor (CAR) are xenobiotic receptors that play crucial roles in the regulation of detoxification processes and hepatic metabolism, including drug-metabolizing enzymes and transporters involved in xenobiotic clearance. Recent research indicates their significant involvement in endogenous signaling pathways, such as lipid, cholesterol, bile acid metabolism, and cell proliferation, highlighting their potential as therapeutic targets for metabolic diseases. Additionally, newly identified ligands of PXR and CAR have demonstrated the ability to enhance chemotherapy efficacy in tumor treatments. This session will review recent advances in understanding how ligands of PXR and CAR modulate endogenous metabolism and discuss their emerging therapeutic applications.

This session will highlight cutting-edge experimental models and technologies transforming our understanding of drug metabolism and pharmacokinetics (DMPK). Due to species differences and limitations of current animal models, there is a growing need for predictive and human-relevant systems and novel models to DMPK. Novel tools are reshaping how we study drug absorption, distribution, metabolism, and excretion. Key topics will include the use of human organoids and liver microtissues as advanced in vitro platforms for evaluating drug metabolism, drug–drug interactions, and toxicity. These 3D models more accurately recapitulating human liver architecture and cellular functions, offering enhanced predictive value compared to traditional 2D cultures and animal systems. The session will also highlight novel animal models designed to investigate the role of specific drug-metabolizing enzymes. In particular, models using targeted protein degradation technologies can selectively modulate enzyme function, helping to overcome the limitations of global knockout approaches and reduce compensatory metabolic effects. Presentations will address how these emerging tools influence enzyme expression, stability, and degradation, providing critical insights into drug behavior and metabolism. This session aims to foster dialogue on how these emerging tools can enhance DMPK in drug development and clinical translation. Speakers from both academia and industry will share their expertise and perspectives on future directions in drug metabolism research and pharmaceutical science.

This symposium delves into the pivotal role of imaging mass spectrometry (IMS) in understanding disease mechanisms and driving drug discovery and development. The first presentation, "From Molecules to Maps," presents innovations in multimodal IMS technologies that facilitate the construction of detailed human tissue atlases, unraveling molecular interactions that underpin health and disease. The second session focuses on cutting-edge workflows for drug metabolism studies, incorporating new analytical technology to improve metabolite identification through advanced ion mobility separation and on-tissue fragmentation techniques. The final talk, "Imaging Mass Spectrometry Unleashed," explores the synergistic integration of IMS with other imaging methodologies to deliver spatial pharmacokinetic-pharmacodynamic (PK-PD) data crucial for enhancing drug discovery efforts. Join us to explore how IMS is reshaping our understanding of molecular landscapes in biomedical and pharmaceutical research.

Xenobiotic receptors, PXR in particular, was discovered nearly 30 years ago. Initially defined as a key regulator of drug metabolizing enzymes, PXR was subsequently found to have more diverse functions. A deeper understanding of the PXR function will help to harness the knowledge in the safe use of medications and management of multiple diseases. The Session will provide case studies to understand structures of PXR and structure-guided design of PXR modulators that include agonists and antagonists, gut microbiome in the homeostasis of PXR ligand availability and receptor activity, and the implication of PXR activation in depression. All speakers are investigators who are active in the topic field. The planned speakers include those from China and USA.

It has become increasingly clear that there is a mutual interaction between diseases and drug metabolism. On one hand, disease or specific physiological conditions can affect the expression and/or activity of drug metabolizing enzymes and transporters. On the other hand, the expression and/or activity of drug metabolizing enzymes and transporters may affect the outcome of the diseases. The Session will provide case studies to understand the mechanism and implications of mutual interaction between diseases and drug metabolism. All speakers are investigators who are active in the topic field.

The endocrine system, through its intricate network of hormones and receptors, serves as the master regulator of human physiology. Its precise function is the fulcrum upon which health balances, governing everything from development and reproduction to metabolism and stress response. Consequently, the dysregulation of these sensitive hormonal pathways—whether arising from endogenous pathology, targeted pharmacological intervention, or inadvertent environmental exposure—represents one of the most significant challenges and opportunities in modern biomedical science. The symposium is structured around three core, interconnected themes. The first addresses The Threat: the pervasive and insidious impact of environmental endocrine-disrupting chemicals (EDCs) on public health. The second explores The Blueprint: the vast, yet largely untapped, potential of natural products as a source of novel hormonal modulators and therapeutic leads. The third pillar details The Strategy: the power of rational, structure-guided synthetic chemistry to develop highly specific and effective therapeutic interventions for endocrine-related diseases. The convergence of these three fields is essential for developing the next generation of diagnostics, preventative strategies, and therapies. By bringing together toxicologists who define the problem, pharmacologists who find clues in nature, and chemists who build the solutions, this symposium will promote an integrated framework for understanding and manipulating hormonal pathways for the betterment of human health.

While cytochrome P450 enzymes involved in drug metabolism receive a lot of attention, a majority of these enzymes function in key pathways controlling physiological homeostasis. Aside from steroidogenic P450 enzymes targeted for cancers, many represent untapped opportunities for treating a wide variety of human diseases. This session focuses on disease treatment via modulation of individual understudied human P450 enzymes. Treatment modalities range from small molecule inhibition to gene delivery to PROTACs. Potential presenters span the range of career stages, 2 genders, both academia and industry, and include 3 speakers hailing from Asia, taking advantage of the meeting location in Hong Kong. Other speaker suggestions welcomed, perhaps especially someone using a P450 regulation approach.

This session will highlight the recent development in mechanism-based pharmacokinetic (PK) modeling to predict drug-drug interactions and the impact of patient-specific factors, such as genetic variations and the physiological changes associated with aging.

Cytochrome P450 enzymes and other microsomal drug-metabolising enzymes have been used in preclinical research in the pharmaceutical industry for many years, However more recently, the catalytic versatility of these enzymes has been explored for catalysing challenging reactions in drug development. This symposium would discuss the current state of this area and explore what is needed for the future to exploit the full potential of xenobiotic-metabolizing enzymes for synthetic purposes. (Note: This would be a target for sponsorship by an enzyme company, such as Codexis or Hypha Discovery, and possibly linked to a lunchtime 'Informercial' type symposium as has been done at meetings of other series, e.g. the ICCP450 meeting in Shizuoka, to great success.)

It has been known for many years that some of the less-well known cytochrome P450 enzymes show polymorphisms that are associated with clinical phenotypes. These associations can provide clues to the physiological role of these 'orphan' enzyme systems. This symposium would start with an overview of the current state of the pharmacogenetics field as it applies to P450s and other enzymes from Andrea Gaedigk, who heads the PharmVar consortium in charge of the CYP allele nomenclature site. The rest of the symposium would cover some notable recent studies that provide insight into the function of orphan P450s, the aetiology of diseases resulting from their absence, and ways in which such diseases can be treated.

Dobzhansky famously commented that 'nothing in biology makes sense except in the light of evolution'. However the evolutionary history of the enzymes we discuss at MDO meetings is usually ignored. This symposium would put microsomes and drug oxidations in the evolutionary context of how these enzyme systems have evolved and the genetic mechanisms underpinning such evolution. (Note: This symposium would offer a contrast to the medical focus of most others while still focusing clearly on the idea of metabolic reactions that occur in microsomes.)