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RAGE/SERT-IN-1 is a potent and orally active advanced glycation end products (RAGE) and serotonin transporter (SERT) inhibitor with IC50s of 8.26 μM and 31.09 nM, respectively. RAGE/SERT-IN-1 exhibits significant neuroprotective effect against Aβ25-35-induced neuronal damage and alleviates depressive behavior of mice. RAGE/SERT-IN-1 can be used for researching the comorbidity of Alzheimer's disease and depression[1]. | [in vivo]
RAGE/SERT-IN-1 (0-10 μM; 60 min) has good liver microsomal stability and does not apparently inhibit main CYP enzymes[1].
RAGE/SERT-IN-1 (100 and 200mg/kg; IP; single dosage) does not cause mice death and not significant change in the ratio of organ-to-body weight at 100 mg/kg[1].
RAGE/SERT-IN-1 (60 mg/kg; PO; single dosage) significantly reduces the immobility time in tail suspension test[1].
RAGE/SERT-IN-1 (60 mg/kg for PO, 10 mg/kg for IV; single dosage) exhibits acceptable pharmacokinetic properties in mice[1].
Pharmacokinetic Parameters of RAGE/SERT-IN-1 in male ICR mice[1].
| PO (60 mg/kg) | IV (10 mg/kg) | | T1/2 (h) | 5.55 | 3.46 | | Cmax (ng/mL) | 4935 | 51745 | | AUC0-∞ (ng/mL·h) | 24684 | 23653 | | CL (mL/min/kg) | | 7.09 | | VSS (L/kg) | | 1037 | | F (%) | 17.1 | |
| Animal Model: | Male ICR mice (24-26 g)[1] | | Dosage: | 100mg/kg and 200mg/kg | | Administration: | IP; single (observed for 2 weeks) | | Result: | All mice were survived and no significant changed in the ratio of organ-to-body weight at a dose of 100 mg/kg. |
| Animal Model: | Male ICR mice[1] | | Dosage: | 60 mg/kg | | Administration: | PO; single dosage | | Result: | Significantly reduced the immobility time in tail suspension test. |
| Animal Model: | Male ICR mice[1] | | Dosage: | 60 mg/kg for PO, 10 mg/kg for IV | | Administration: | PO and IV; single dosage | | Result: | Exhibited acceptable pharmacokinetic properties in mice. |
| [References]
[1] Zhang C, Wang L, Xu Y, et al. Discovery of novel dual RAGE/SERT inhibitors for the potential treatment of the comorbidity of Alzheimer's disease and depression. Eur J Med Chem. 2022;236:114347. DOI:10.1016/j.ejmech.2022.114347 |
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