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Solute carriers (SLCs) represent the largest group of membrane transporters in the human genome. They play a central role in controlling the compartmentalization of metabolism and most of this superfamily is linked to human disease. Despite being in general considered druggable and attractive therapeutic targets, many SLCs remain poorly annotated, both functionally and structurally. The aim of this review is to provide an overview of functional and structural parameters of SLCs that play important roles in their druggability. To do this, the authors provide an overview of experimentally solved structures of human SLCs, with emphasis on structures solved in complex with chemical modulators. From the functional annotations, the authors focus on SLC localization and SLC substrate annotations. Recent progress in the structural and functional annotations allows to refine the SLC druggability index. Particularly the increasing number of experimentally solved structures of SLCs provides insights into mode-of-action of a significant number of chemical modulators of SLCs.

Structural and functional annotation of solute carrier transporters: implication for drug discovery