Affiliation:
1. Membrane Transport Discovery Lab, Department of Nephrology and Hypertension, and Department for BioMedical Research, Inselspital, University of Bern, Freiburgstrasse 15, CH-3010 Bern, Switzerland
Abstract
Transmembrane transport of small organic and inorganic molecules is one of the cornerstones of cellular metabolism. Among transmembrane transporters, solute carrier (SLC) proteins form the largest, albeit very diverse, superfamily with over 400 members. It was recognized early on that xenobiotics can directly interact with SLCs and that this interaction can fundamentally determine their efficacy, including bioavailability and intertissue distribution. Apart from the well-established prodrug strategy, the chemical ligation of transporter substrates to nanoparticles of various chemical compositions has recently been used as a means to enhance their targeting and absorption. In this review, we summarize efforts in drug design exploiting interactions with specific SLC transporters to optimize their therapeutic effects. Furthermore, we describe current and future challenges as well as new directions for the advanced development of therapeutics that target SLC transporters.
Funder
Swiss National Science Foundation
Novartis Foundation
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference532 articles.
1. Sodium-Coupled Glucose Transport, the SLC5 Family, and Therapeutically Relevant Inhibitors: From Molecular Discovery to Clinical Application;Gyimesi;Pflugers Arch.,2020
2. The Human ATP-Binding Cassette (ABC) Transporter Superfamily;Dean;Hum. Mutat.,2022
3. Relevance of ABC Transporters in Drug Development;Nwabufo;Curr. Drug Metab.,2022
4. The ABCs of Membrane Transporters in Health and Disease (SLC Series): Introduction;Hediger;Mol. Asp. Med.,2013
5. Gyimesi, G., and Hediger, M.A. (2022). Systematic in Silico Discovery of Novel Solute Carrier-like Proteins from Proteomes. PLoS One, 17.
Cited by
9 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献