RAGE/SERT-IN-1 is a potent, orally active inhibitor of advanced glycation end products (RAGE) and serotonin transporter (SERT), with IC50 values of 8.26 μM and 31.09 nM, respectively. It demonstrates significant neuroprotective effects against Aβ25-35-induced neuronal damage and alleviates depressive behavior in mice. RAGE/SERT-IN-1 is useful for research on the comorbidity of Alzheimer's disease and depression [1].

RAGE/SERT-IN-1 (compound 12) at concentrations of 1-20 μM, applied for 24 hours, does not significantly affect the viability of SH-SY5Y cells [1].

RAGE/SERT-IN-1 (0-10 μM; 60 min) shows robust liver microsomal stability and negligible inhibition of primary CYP enzymes [1]. Administered intraperitoneally (IP) at 100 and 200 mg/kg, it causes no mortality or significant organ-to-body weight ratio changes at 100 mg/kg in mice [1]. A single oral dose (60 mg/kg) significantly reduces immobility time in the tail suspension test, suggesting antidepressant-like activity [1]. Additionally, RAGE/SERT-IN-1 administered orally (60 mg/kg) and intravenously (IV) (10 mg/kg) shows favorable pharmacokinetic profiles in mice, with a half-life (T 1/2) of 5.55 and 3.46 hours, maximum concentration (C max) of 4935 and 51745 ng/mL, area under the curve (AUC 0-∞) of 24684 and 23653 ng/mL·h, clearance (CL) of 7.09 mL/min/kg, steady-state volume of distribution (V SS) of 1037 L/kg, and bioavailability (F) of 17.1% [1].