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The Transporter Map project addresses a critical gap in transporter drug discovery through an innovative technology platform that enables comprehensive, family-wide screening of substrates and inhibitors. Cellular transporters control the movement of nutrients and drugs across cell membranes, with approximately 1500 genes dedicated to their functions in the human genome. Despite their role in virtually every cellular process and connection to numerous diseases, they have been largely untapped for treating human disease. One major challenge for developing drugs for transporters has been the lack of robust assay technology for family-wide transporter screening. While other successful target classes such as G protein-coupled receptors (GPCRs) benefit from streamlined assay development, where one assay fits many targets, transporter assays have required specialized, individual approaches for each transporter, making assay development expensive and tedious. This has created a significant disparity in drug discovery outcomes. Despite similar disease relevance, only 5% of transporters are targeted by approved drugs, compared to 24% of GPCRs. Transporter Map aims to close this technology gap by combining a library of genetically-encoded biosensors with an overexpression library of the entire transporter family. When a cell encounters a substrate compatible with its overexpressed transporter, it takes it up, triggering a fluorescence change in one or multiple biosensors. This fluorescence change enables the enrichment of cells expressing that transporter and allows identification of specific transporters responsible for substrate uptake. The Transporter Map platform transforms transporter research by providing a pooled screening method previously unavailable to the field and has potential to significantly accelerate drug discovery efforts.
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