ECSI#6 is the first uncompetitive serotonin transporter (SERT) inhibitor. Inhibition of serotonin uptake by ECSI#6 was enhanced with increasing serotonin concentration. Conversely, the KM for serotonin was lowered by augmenting ECSI#6. ECSI#6 bound with low affinity to the outward-facing state of SERT but with increased affinity to a potassium-bound state. ECSI#6 also acted as a pharmacochaperone: cellular preincubation with ECSI#6 restored export from the endoplasmic reticulum (ER) and substrate transport by a misfolded SERT variant.

KEYWORDS: ECSI#6 | SERT inhibitor | CAS [860456-56-0] | Serotonin |SERT | Inhibitor | Proteins