DPTIP is an inhibitor of neutral sphingomyelinase 2 (nSMase2; IC50 = 30 nM).1 It is selective for nSMase2 over alkaline phosphatase (ALP) and acid sphingomyelinase (IC50s = >100 ?M for both). DPTIP reduces viral yield in Vero and HeLa cells infected with West Nile virus (EC50s = 0.26 and 2.81 ?M, respectively) or Zika virus (EC50s = 1.56 and 1.84 ?M, respectively).2 It inhibits the secretion of extracellular vesicles from primary mouse astrocytes activated by FBS withdrawal in a concentration-dependent manner and prevents serum deprivation-induced astrocyte activation in primary rat astrocytes when used at a concentration of 10 ?M.1 DPTIP (10 mg/kg) reduces IL-1β-induced extracellular vesicle release from astrocytes and decreases neutrophil infiltration to the brain in a model of inflammation-induced brain injury using GFAP-GFP mice. It reduces hepatic levels of chemokine (C-C motif) ligand 2 (Ccl2), Tnf-α, Il-6, and Il-1β in the same model.
References:
[1]. Rojas, C., Barnaeva, E., Thomas, A.G., et al.DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammationSci. Rep.817715(2018).
[2]. ?lvarez-Fernández, H., Mingo-Casas, P., Blázquez, A.B., et al.Allosteric inhibition of neutral sphingomyelinase 2 (nSMase2) by DPTIP: From antiflaviviral activity to deciphering its binding site through in silico studies and experimental validationInt. J. Mol. Sci.23(22)13935(2022).