Allosteric modulation of the solute carrier transporter SLC39A8 potentiates manganese and cadmium uptake.

ABSTRACT: Solute carrier (SLC) transporters govern the selective transport of diverse molecules across cell membranes, controlling fundamental metabolic and cellular processes. Despite genetic evidence implicating SLC transporters in a variety of human diseases, this family of proteins represents an underexplored target class for therapeutic drug discovery. Here, we discovered a selective potentiator of SLC39A8, a metal transporter associated with inflammatory bowel disease, schizophrenia, and cardiovascular and metabolic disorders. We conducted a drug repurposing screen, identifying efavirenz as a potentiator of manganese and cadmium uptake by SLC39A8 and subsequently generated structure-activity relationships to guide design of analogs. Computational pocket identification methodology and molecular

SUBMITTER: Damm-Ganamet KL 

PROVIDER: S-EPMC12578388 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature