Membrane transporters in drug development and as determinants of precision medicine

• Published in: Nature reviews. Drug discovery Vol. 23; no. 4; pp. 255 - 280
• Main Authors: Galetin, Aleksandra, Brouwer, Kim L. R., Tweedie, Donald, Yoshida, Kenta, Sjöstedt, Noora, Aleksunes, Lauren, Chu, Xiaoyan, Evers, Raymond, Hafey, Michael J., Lai, Yurong, Matsson, Pär, Riselli, Andrew, Shen, Hong, Sparreboom, Alex, Varma, Manthena V. S., Yang, Jia, Yang, Xinning, Yee, Sook Wah, Zamek-Gliszczynski, Maciej J., Zhang, Lei, Giacomini, Kathleen M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2024; Nature Publishing Group
• Subjects: 631/154/436/108; 692/308/153; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer Research; Consortia; Drug Development; Drug Interactions; Farmaceutisk vetenskap; Humans; Medicinal Chemistry; Membrane Transport Proteins; Molecular Medicine; Pharmaceutical Sciences; Pharmacology/Toxicology; Precision Medicine; Review Article
• ISSN: 1474-1776; 1474-1784; 1474-1784
• DOI: 10.1038/s41573-023-00877-1

The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug–drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions. Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.