sms2 in 2

SMS2-IN-2 (SMS2 inhibitors) is a potent, selective and orally active sphingomyelin synthase 2 (SMS2) inhibitor, (IC50s of 100 and 56 μM for SMS2 and SMS1, respectively). SMS2-IN-2 has anti-chronic inflammatory activity.

SMS2-IN-1 is an effective and highly selective sphingomyelin synthetase 2 (SMS2) inhibitor with IC50 of 6.5 nM and Kd of 37 nM. Sms2-in-1 is 150 times more selective to SMS2 than SMS1 (IC50 is 1000 nM).

Ceramide phosphoethanolamine (CPE) is an analog of sphingomyelin that contains ethanolamine rather than choline as the head group. It is the principal membrane phospholipid in invertebrates such as Drosophila, which lacks sphingomyelin. It is only produced in small amounts in mammalian cells, accounting for approximately 0.02 mol% of total phospholipids in mouse testis and brain. In Drosophila, CPE is biosynthesized by CPE synthase from ceramide and cytidine diphosphate-ethanolamine in the Golgi lumen. In mammals, it is biosynthesized by sphingomyelin synthase 2 (SMS2) in the plasma membrane and by sphingomyelin synthase-related protein (SMSr) in the endoplasmic reticulum (ER). In Drosophila, CPE has a role in glial ensheathment of axons. Disrupting CPE synthesis by depleting SMSr in vitro in mammalian cells leads to an accumulation of ER ceramides, which are then mislocalized to the mitochondria, inducing apoptosis. However, ceramide levels are not altered in transgenic mice lacking SMSr catalytic activity. CPEs (bovine) is a mixture of CPEs with variable N-acyl chain lengths.