Membrane transporters in drug development and as determinants of precision medicine

Aleksandra Galetin; Kim L.R. Brouwer; Donald Tweedie; Kenta Yoshida; Noora Sjöstedt; Lauren Aleksunes; Xiaoyan Chu; Raymond Evers; Michael J. Hafey; Yurong Lai; Pär Matsson; Andrew Riselli; Hong Shen; Alex Sparreboom; Manthena V.S. Varma; Jia Yang; Xinning Yang; Sook Wah Yee; Maciej J. Zamek-Gliszczynski; Lei Zhang; Kathleen M. Giacomini

doi:10.1038/s41573-023-00877-1

Membrane transporters in drug development and as determinants of precision medicine

Aleksandra Galetin^*, Kim L.R. Brouwer, Donald Tweedie, Kenta Yoshida, Noora Sjöstedt, Lauren Aleksunes, Xiaoyan Chu, Raymond Evers, Michael J. Hafey, Yurong Lai, Pär Matsson, Andrew Riselli, Hong Shen, Alex Sparreboom, Manthena V.S. Varma, Jia Yang, Xinning Yang, Sook Wah Yee, Maciej J. Zamek-Gliszczynski, Lei ZhangKathleen M. Giacomini^*

^*Corresponding author for this work

Pharmacy

Research output: Contribution to journal › Review article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	255-280
Number of pages	26
Journal	Nature Reviews Drug Discovery
Volume	23
Issue number	4
Early online date	24 Jan 2024
DOIs	https://doi.org/10.1038/s41573-023-00877-1
Publication status	Published - 1 Apr 2024

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Galetin, A., Brouwer, K. L. R., Tweedie, D., Yoshida, K., Sjöstedt, N., Aleksunes, L., Chu, X., Evers, R., Hafey, M. J., Lai, Y., Matsson, P., Riselli, A., Shen, H., Sparreboom, A., Varma, M. V. S., Yang, J., Yang, X., Yee, S. W., Zamek-Gliszczynski, M. J., ... Giacomini, K. M. (2024). Membrane transporters in drug development and as determinants of precision medicine. Nature Reviews Drug Discovery, 23(4), 255-280. https://doi.org/10.1038/s41573-023-00877-1

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title = "Membrane transporters in drug development and as determinants of precision medicine",

abstract = "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.",

author = "Aleksandra Galetin and Brouwer, {Kim L.R.} and Donald Tweedie and Kenta Yoshida and Noora Sj{\"o}stedt and Lauren Aleksunes and Xiaoyan Chu and Raymond Evers and Hafey, {Michael J.} and Yurong Lai and P{\"a}r Matsson and Andrew Riselli and Hong Shen and Alex Sparreboom and Varma, {Manthena V.S.} and Jia Yang and Xinning Yang and Yee, {Sook Wah} and Zamek-Gliszczynski, {Maciej J.} and Lei Zhang and Giacomini, {Kathleen M.}",

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doi = "10.1038/s41573-023-00877-1",

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Galetin, A, Brouwer, KLR, Tweedie, D, Yoshida, K, Sjöstedt, N, Aleksunes, L, Chu, X, Evers, R, Hafey, MJ, Lai, Y, Matsson, P, Riselli, A, Shen, H, Sparreboom, A, Varma, MVS, Yang, J, Yang, X, Yee, SW, Zamek-Gliszczynski, MJ, Zhang, L & Giacomini, KM 2024, 'Membrane transporters in drug development and as determinants of precision medicine', Nature Reviews Drug Discovery, vol. 23, no. 4, pp. 255-280. https://doi.org/10.1038/s41573-023-00877-1

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T1 - Membrane transporters in drug development and as determinants of precision medicine

AU - Galetin, Aleksandra

AU - Brouwer, Kim L.R.

AU - Tweedie, Donald

AU - Yoshida, Kenta

AU - Sjöstedt, Noora

AU - Aleksunes, Lauren

AU - Chu, Xiaoyan

AU - Evers, Raymond

AU - Hafey, Michael J.

AU - Lai, Yurong

AU - Matsson, Pär

AU - Riselli, Andrew

AU - Shen, Hong

AU - Sparreboom, Alex

AU - Varma, Manthena V.S.

AU - Yang, Jia

AU - Yang, Xinning

AU - Yee, Sook Wah

AU - Zamek-Gliszczynski, Maciej J.

AU - Zhang, Lei

AU - Giacomini, Kathleen M.

PY - 2024/4/1

Y1 - 2024/4/1

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AB - 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.

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Membrane transporters in drug development and as determinants of precision medicine

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