SERT-IN-2

SERT-IN-2 is a potent SERT inhibitor (IC50=0.58 nM) with promising anti-depression efficacy. SERT-IN-2 shows good bioavailability of 83.28% in rats. SERT-IN-2 can cross the blood-brain barrier[1].

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> Serotonin Transporter

IC50: 0.58 nM (SERT)[1]

SERT-IN-2 (DH4) (2.5 mg/kg, 5 mg/kg; 口服或静脉注射; 单次剂量) 显示高血浆暴露和口服生物利用度在狗和大鼠[1]。 SERT-IN-2 (10 mg/kg; 腹腔注射; 单次剂量) 可以穿过 SD 大鼠的血脑屏障[1]。 SERT-IN-2 (1-10 mg/kg; 腹腔注射; 单次剂量) 抑制 5-羟色胺的摄取，并有效拮抗大鼠下丘脑中 p-chloroamphetamine (PCA) 诱导的 5-羟色胺的消耗[1]。 SERT-IN-2 (1-10 mg/kg; 静脉注射; 试验前给药 3 次) 对大鼠有抗抑郁作用，并呈剂量依赖性地减少强迫游泳试验 (FST) 的不动次数[1]。 药代动力学分析[1] Route Dose (mg/kg) Cmax (ng/mL) AUC(0-t) (ng·h/mL) T1/2 (h) Vss (L/kg) Cl (L/h/kg) F (%) Rat IV 1 193 1340 7.53 6.41 11.6 / PO 2.5 180 2790 7.28 / / 83.28 Dog IV 1 520 2820 4.39 3.4 5.14 / PO 5 794 7540 16.4 / / 53.5

[1]. Wang ZZ, et al. Deciphering Nonbioavailable Substructures Improves the Bioavailability of Antidepressants by Serotonin Transporter. J Med Chem. 2023 Jan 12;66(1):371-383.