hMAO-B-IN-2

hMAO-B-IN-2 (compound 6j) is an orally active, potent, selective and BBB penetrated and competitive reversible hMAO-B inhibitor, with an IC50 of 4 nM. hMAO-B-IN-2 shows low toxicity and good neuroprotective effects in SH-SY5Y cell. hMAO-B-IN-2 can be used for alzheimer’s disease research[1].

Signaling Pathways >> Neuronal Signaling >> Monoamine Oxidase

Research Areas >> Neurological Disease

MAO-B:4 nM (IC50)

hMAO-B-IN-2 (compound 6j) (0-100 μM, 15 min) exhibits potent inhibitory activity, with IC50 values of 4 nM (hMAO-B) and 6.04 nM (hMAO-A), respectively[1]. hMAO-B-IN-2 (30 min) is a reversible MAO-B inhibitor, the activity of MAO-B enzyme was restored to about 82% and 45% after compound 6j dilution to 0.1 × IC50 and 1 × 50, respectively[1]. hMAO-B-IN-2 (25 μM, 48 h) exhibits remarkable inhibitory activities against MAO-B, had good inhibition property of Aβ self-induce aggregation (40.78 ± 6.27%)[1]. hMAO-B-IN-2 (0-100 μM, 24 h) shows non-toxic at the concentrations of 25 μM[1]. hMAO-B-IN-2 (0-25 μM, 24 h) has neuroprotective capability against neurodegeneration disease, and increases cell survival rates in a dose-dependent manner[1]. Cell Cytotoxicity Assay Cell Line: SH-SY5Y neuroblastoma cell[1] Concentration: 0, 6.25, 12.5, 25, 50, 100 μM Incubation Time: 24 h Result: Showed non-toxic at the concentrations of 25 μM.

hMAO-B-IN-2 (compound 6j) (Sprague-Dawley rats; 3 mg/kg, IV; 10 mg/kg, PO; once) has acceptable pharmacokinetic properties[1]. Pharmacokinetic Parameters of hMAO-B-IN-2 in male Sprague-Dawley rats[1]. Parameters IV (3 mg/kg) PO (10 mg/kg) T1/2 (h) 1.02 ± 0.17 1.33 ± 0.16 Tmax (h) 0.3 Cmax (μg/L) 639.29 ± 89.06 142.17 ± 72.21 AUC0-inf (μg/L∗h) 247.74 ± 11.48 268.49 ± 69.72 CL (L/h/kg) 3.33 ± 0.15 F (%) 36.10% Animal Model: Sprague-Dawley rats (male, 220±20 g)[1] Dosage: 3 mg/kg (IV), 10 mg/kg (PO) Administration: IV, PO (Pharmacokinetic Analysis) Result: Had acceptable pharmacokinetic properties, and showed a high maximal concentration, appropriate half-life, and good oral bioavailability.

[1]. Xie SS, Liu J, Tang C, et al. Design, synthesis and biological evaluation of rasagiline-clorgyline hybrids as novel dual inhibitors of monoamine oxidase-B and amyloid-β aggregation against Alzheimer's disease. Eur J Med Chem. 2020;202:112475.