Potent and selective sphingomyelin phosphodiesterase (N-SMase2) inhibitor (IC50 = 30 nM). Exhibits no inhibition of related enzymes alkaline phosphatase, phosphomonoesterase or acid sphingomyelinase. Inhibits extracellular vesicle (EV) release in primary astrocyte cultures and in vivo. Attenuates IL-1β-induced astrocyte-derived EV release in a mouse model of brain injury and suppresses infiltration of immune cells into the brain. Metabolically stable and brain penetrant.
Rojas et al (2018) DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammation. Sci.Rep. 8 17715 PMID:30531925