ASM-IN-2 is an effective ASM inhibitor, with an IC50 value of 0.87 μM. It engages various antidepressant mechanisms associated with the reduction of ceramides and has demonstrated significant antidepressant effects in a CUMS-induced rat model, promising for research in antidepressant therapies.

PLC:0.87 μM

ASM-IN-2 demonstrates the highest activity in binding to ASM, with an IC50 value of 0.87 μM. In experiments using the CCK8 assay to evaluate its anti-proliferative effects on human neuroblastoma SH-SY5Y cells, ASM-IN-2 exhibits slight cytotoxicity at a higher concentration of 100 μM (cell viability over 78%).

"ASM-IN-2 (1,10 MG/KG, i.v.;i.p.) is rapidly absorbed in male ICR mice, achieving high peak concentrations (Cmax = 4204.13 NG/ML) within a quarter hour (Tmax = 0.25 h) and demonstrating moderate bioavailability (F = 39.59%), making it suitable for use in antidepressant research.

In addition, ASM-IN-2 administered at doses of 6, 12, and 24 MG/KG via i.p. for 10 days significantly reduced immobility time in both the Forced Swim Test (FST) and the Tail Suspension Test (TST), surpassing the effects observed with Fluoxetine at 12 MG/KG. This compound enhances the expression of BDNF and levels of the myelin lipid ceramide in the cerebral cortex, while reducing oxidative stress by inhibiting AMS activity. In the CUMS mouse model, ASM-IN-2 displayed dose-dependent reductions in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, attenuating inflammatory responses in mouse serum. Moreover, the substance notably increased serotonin (5-HT) levels in the hippocampal tissue of mice, enhancing antidepressant activity through ASM inhibition."