ISSX Webinars are presented by internationally recognized scientists on a variety of subjects relevant to the field. The ISSX Continuing Education Committee is charged with the responsibility for reviewing these educational offerings and setting the webinar schedule.

When you purchase a webinar registration, you will receive access to speaker slides, the recorded lecture, and the Q&A session.

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    The resurgence of covalent inhibitors as a viable therapeutic approach continues to expand and positively impact patients, particularly for targets previously considered undruggable. The application of targeted covalent inhibitor (TCI) strategies is broadening the range of druggable targets. Adopting and implementing appropriate computational and experimental paradigms will facilitate the design and selection of clinical candidates throughout the drug discovery and development process. While well-defined steps for the development of targeted covalent drugs are evolving, this presentation will outline a general strategy for the discovery and development of TCIs. Additionally, pharmacokinetic/pharmacodynamic (PK/PD) and efficacy mechanistic models for covalent drugs will be discussed. These mechanistic PK/PD/efficacy models derived from pre-clinical and clinical experience will enhance our understanding of the pharmacokinetic and pharmacodynamic interplay and assist in designing next-generation covalent drugs.

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    Join us for an exciting webinar spotlighting emerging research led by African trainees tackling some of the continent’s most pressing health challenges. This session, with attendees drawn from the recently concluded ISSX Africa workshop, will feature four dynamic presentations exploring complex pharmacokinetics drug-drug interactions (DDI) and modelling in African patients.

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    Quantitative, Translational, & ADME Sciences (QTAS), Abbvie Inc., North Chicago, IL, USA Abstract: Compounds exhibiting low metabolic clearance are often favored to improve pharmacokinetic profiles and decrease dose. To predict clearance, common experimental techniques include incubations with liver microsomes or cryopreserved hepatocytes in suspension. Hepatocytes in suspension are generally favored as they enable testing of a nearly comprehensive set of metabolic enzymes. However, suspension hepatocytes gradually lose viability in culture, limiting ability to test stable compounds that require longer incubations. Plated hepatocytes will survive for days but lose most drug metabolizing enzyme capacity within 48 hours. In this presentation, methods to overcome loss of phenotype (or increase in assay analytical sensitivity) will be presented. Also, the performance of the models with up to 50 compounds of varying physical chemical properties for predicting clearance will be discussed. The models include hepatocyte suspensions, co-cultures with mouse fibroblasts, tri-cultures with human stromal and endothelial cells, high well density spheroids, and finally a “pre-load” model using mono-culture hepatocytes.

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    This webinar aims to present novel research on hepatic transport zonation in metabolic dysfunction-associated steatohepatitis (MASH) and the interaction of Δ9-tetrahydrocannabinol (THC) with hepatic and placental transporters, thereby enhancing our understanding of THC disposition in pregnant women. This includes elucidating the identity of transporters influencing the disposition of THC and its metabolites, and the application of a novel liver PBPK model that incorporates zonal distribution of hepatic transporters to predict disease-related changes in statin disposition for patients with MASH.

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    This webinar is intended to provide drug developers with a comprehensive understanding of the unique DMPK challenges posed by oligonucleotide therapeutics and practical strategies to overcome them. Attendees will gain insights into advanced delivery platforms, customized pharmacokinetic approaches, and specialized administration methods, particularly for CNS-targeting oligonucleotides. By exploring real-world examples and established methodologies, the webinar aims to empower researchers to accelerate preclinical development and enhance their success in drug development and regulatory submissions.

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    This webinar will introduce dynamic free fraction (fd) as a new concept characterizing drug protein binding and demonstrate the utility of fd in hepatic clearance mediated by CYP and OATP transporter.

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    This webinar is intended to raise the awareness of complicated scenario where drug-drug-disease interaction occurs and how to evaluate the PK of drugs using PBPK to inform the optimal use of drugs in such patient group.

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    In this webinar we will discuss efforts for improving the global underrepresentation of African genetics in science. We will further explore the current landscape and challenges in realizing an African hepatic modeling platform - with a specific focus on the development of hiPSC models that can better recapitulate hepatic function.

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    This symposium/webinar is intended to educate ADME scientists on MPS technology and its potential to generate clinically translatable data.

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    The human genome comprises approximately 20,000 protein-coding genes and over 900 million variants according to dbSNP. Systematic understanding of the impact of genomic alterations in humans is critical for the development of effective medicines. However, it is simply not feasible to study every single variant in detail. This challenge extends to the analysis of how pharmacogenes are affected by genetic polymorphisms, as it is impossible to study the impact of every individual single nucleotide polymorphisms/variations (SNPs/SNVs) of pharmacogenes in human clinical trials. Yet, understanding drug metabolism and pharmacokinetics is crucial for assessing drug efficacy and safety. To minimize harmful side effects from drugs while maximizing their therapeutic effectiveness in each patient or group of patients, we would need to understand the effects of population specific SNPs in pharmacogenes and drug-enzyme interactions. To date the effect of non-synonymous SNPs, more specifically missense mutations, at the protein level is poorly studied in pharmacogenomics research. We previously proposed a post-hoc analysis approach of molecular dynamics (MD) simulations using dynamic residue network (DRN) analysis to consider the dynamic nature of functional proteins and protein-drug complexes and to probe the impact of mutations and their allosteric effects. This talk will discuss the computational approaches and tools that we have developed over the years with applications to pharmacogenomics.