Inhibition of the Alanine-Serine-Cysteine-1 Transporter by BMS-466442.
Ivan R TorrecillasSusana Conde-CeideAna Isabel de LucasAránzazu Garcı A MolinaAndres A TrabancoHilde LavreysenLeonardo PardoGary John TresadernPublished in: ACS chemical neuroscience (2019)
Experiment and modeling were combined to understand inhibition of the alanine-serine-cysteine-1 (asc1) transporter. The structure-activity relationship (SAR) was explored with synthesis of analogues of BMS-466442. Direct target interaction and binding site location between TM helices 6 and 10 were confirmed via site directed mutagenesis. Computational modeling suggested the inhibitor binds via competitive occupation of the orthosteric site while also blocking the movement of TM helices that are required for transport.