ASM-IN-2 (Compound 46) is a potent ASM inhibitor with an IC 50 value of 0.87 μM, displaying good drug-like properties. ASM-IN-2 involves in multiple antidepressant mechanisms of actionin, which are associated with a decline of ceramide. It demostrates remarkable antidepressant effects in the CUMS-induced mouse, which is promising for research in the field of antidepressant drugs.