Hey Adam, I know that it acts on sphingomyelinases, however I'm curious to how specific this sphingomyelinase is against exosome-specific transport...thanks :)
I know that this drug inhibit the ceramide synthesis, and the ceramide is a essencial lipid for a subtype of exosome biogenesis in multivesicular bodies.
Its a tricky drug to use (very hydrophobic) but it does inhibit NSMase2, at least partially. We have not used it to block exosome release but others seem to get good results
As noted above, GW4869 is reported to inhibit nSMase2 - but can also affect other neutral sphingomyelinase isoforms it seems. A recent study found that both GW and siRNA knockdown of nSMase2 decreased exosome secretion but actually increased microvesicle secretion.
we find that knockdown of NSMase does increase EV secretion The fro/fro fragillis ossium mouse develops slowly and has problems with bones due to reduced ceramics and poor mineralization--but they seem to catch up with littermates later on. NSMase is not the whole story but is a part of it