KARI 201

KARI 201 (KARI-201) is a dual-action small molecule that exhibit highly selective inhibition effects on Acid sphingomyelinase (ASM), and act as a ghrelin receptor agonist.KARI 201 is a competitive inhibitor that binds to the active site of ASM.Incorporation of KARI 201 into ASM was decreased with increasing concentrations of sphingomyelin, yielding KM values of 332.5, 433.9, and 572.6 μM at 1, 10, and 100 μM KARI 201, respectively.Administration of KARI 201 reduces amyloid pathology and restores cognitive impairment in APP/PS1 mice.KARI 201 ameliorates defective autophagy degradation by regulating lysosomal biogenesis in neurons.KARI 201 is a ghrelin receptor agonist and improves hippocampal neurogenesis and synapse plasticity.

1. Wang M, et al. Proc Natl Acad Sci U S A. 2022 Jan 18;119(3):e2115082119.