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- W2046677279 abstract "The blood-brain barrier (BBB) limits the uptake of most drugs by brain, and the traditional approach to the BBB problem is the use of medicinal chemistry to increase drug lipid solubility, and increase lipid-mediated transport across the BBB. This review advocates a new model to CNS drug discovery of BBB-penetrating small molecules, whereby drug candidates are screened for carrier-mediated transport (CMT) across the BBB.CMT systems are expressed by genes within the Solute Carrier (SLC) Transporter Gene Family, which now totals > 400 transporter genes. Emphasis is placed on reconciliation of the substrate transporter profile (STP) of BBB transport in vivo with the STP of the cloned SLC transporter in vitro. This reconciliation is crucial to the identification, from sometimes a large number of candidates, of the respective SLC transporter that is responsible for BBB transport in vivo for a given class of nutrients.Dual track screening of a small molecule library for drugs that have the dual properties of affinity for a neural cell drug receptor target, and affinity for a BBB CMT transporter target, can lead to a revolution in how small molecule drugs are identified in CNS drug discovery programs." @default.
- W2046677279 created "2016-06-24" @default.
- W2046677279 creator A5073892880 @default.
- W2046677279 date "2015-05-02" @default.
- W2046677279 modified "2023-09-25" @default.
- W2046677279 title "Blood–brain barrier endogenous transporters as therapeutic targets: a new model for small molecule CNS drug discovery" @default.
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- W2046677279 doi "https://doi.org/10.1517/14728222.2015.1042364" @default.
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