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Chemical Biology: Approaches to Drug Discovery and Development to Targeting Disease by Natanya Civjan

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Chapter 7: Drug Transport in Living Systems

Yael Elbaz

Shimon Schuldiner

Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Department of Biologic Chemistry, Jerusalem, Israel

Living organisms are constantly assailed by a host of harmful chemicals from the environment. Because of the diversity of these “xenobiotics”, cellular survival mechanisms must deal with an immense variety of molecules. Polyspecific drug transporters supply one such strategy. They recognize a wide range of dissimilar substrates that may differ in structure, size, or electrical charge, and they actively remove them from the cytoplasm. As such, these transporters provide an essential survival strategy for the organism. However, given that the substrates of these multispecific transporters include many antibiotics as well as antifungal and anticancer drugs, they are associated with the phenomenon of multidrug resistance (MDR) that poses serious problems in the treatment of cancers and infectious diseases, and some of them are coined multidrug transporters (MDTs). As expected from their central role in survival, these transporters are ubiquitous, and in many genomes, several genes coding for putative MDTs have been identified. MDTs are found in evolutionary unrelated membrane transport protein families, which suggests that they might have developed independently several times during the course of evolution. In this review, we discuss some basic concepts regarding drug transport from ...

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