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• W1546006022 abstract "In contrast to many treatments in non-infectious disease, which often act on extracellular targets such as cell surface receptors, anti-microbial chemotherapy almost invariably requires the uptake of the drug by the pathogen, in order to reach an intracellular target. The pathogen itself is often also resident within a host cell. Drug efficacy, therefore, is as much dependent on the efficient entry into the right cells as on selectivity at the target level. Entry into target cells and/or passage to target cells through host cells may be dependent on diffusion across the relevant biological membranes or on transport proteins located in these membranes. The former process is the norm for lipophilic compounds, whereas the latter is required for hydrophilic compounds, which do not appreciably diffuse across membranes. From a drug development perspective, these issues should be considered early-on and latest in the lead optimization strategy, as both options have advantages and drawbacks, which will be discussed in this chapter. Perhaps the most important issue is that transporters are highly specific in what they transport, whereas diffusion is a non-specific process, whereby a compound indiscriminately crosses any membrane dependent only on the concentration gradient. The selectivity of transport proteins can be a barrier to drug development, disallowing highly active enzyme inhibitors from entering target cells, or can allow the development of cleverly targeted drugs by engineering recognition motifs for transporters expressed only by the pathogen, allowing selective uptake and accumulation by the pathogen. In cases when this transport is energy-dependent, the drug may be concentrated against the concentration gradient. Conversely, the functional loss of such a transporter by the pathogen has often been the cause of drug resistance." @default.
• W1546006022 created "2016-06-24" @default.
• W1546006022 creator A5005584147 @default.
• W1546006022 creator A5065269966 @default.
• W1546006022 date "2013-04-04" @default.
• W1546006022 modified "2023-09-30" @default.
• W1546006022 title "Transporters in Anti‐Parasitic Drug Development and Resistance" @default.
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• W1546006022 doi "https://doi.org/10.1002/9783527670383.ch18" @default.
• W1546006022 hasPublicationYear "2013" @default.
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