Dynamic extracellular vestibule of human SERT: Unveiling druggable potential with high-affinity allosteric inhibitors

• DOI: 10.1073/pnas.2304089120
• Publication Date: 2023-10-04T16:22:06Z
• Authors: Kristine Salomon; Ara M. Abramyan; Per Plenge; Lingle Wang; Christoffer Bundg...; Benny Bang-Andersen; Claus J. Loland; Lei Shi
• Keywords: Druggability

The serotonin transporter (SERT) tightly regulates synaptic levels and has been the primary target of antidepressants. Binding inhibitors to allosteric site human SERT (hSERT) impedes dissociation antidepressants bound at central may enhance efficacy such potentially reduce their dosage side effects. Here, we report identification a series high-affinity hSERT in unique scaffold, with lead compound, Lu AF88273 (3-(1-(2-(1