ArticleACS pharmacology & translational science2026
Target Class Repurposing Across Membrane Transporter Families Provides Privileged Ligands to Address Specific and Undruggable Pharmacological Targets.
Article in ACS pharmacology & translational science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Altogether, 60-70% of the ATP-binding cassette (ABC) and solute carrier (SLC) transporters can currently not be targeted by drugs, despite their involvement in human diseases. The design of potential drug candidates relies on hit identification and subsequent optimization with regard to selectivity and specificity. However, these workflows ultimately fail if no hit molecules can be found. We pursued a strategy of rational discovery of hit molecules for 'undruggable' ABC and SLC transporters based on polypharmacology as an alternative approach in the drug development repertoire. The 42 most polypharmacological ABC transporter modulators were profiled against eight specific (NAT, DAT, and SERT) and polyspecific (OCT1-3, MATE1-2K) SLCs. The general hit rate increased expectedly with the degree of polyspecificity, ranging from 0 to 9.52% (NAT, DAT, SERT) to 19.0-52.4% (OCT1-3, MATE1-2K). Striking was the hit rate for potent drugs, which was highest for the specific transporter SERT (75.0%); additionally, pranlukast (
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