2-Palmitoyl glycerol (2-PG) has been isolated along with the potent endocannabinoid 2-arachidonoyl glycerol (2-AG) from various tissues.1 Although 2-PG displays no intrinsic agonist activity on CB1 or CB2 receptors, it does potentiate the ability of 2-AG to inhibit adenylyl cyclase. 2-PG also potentiates the analgesic, hypokinetic, and anxiolytic effects of 2-AG in mice. This “entourage” effect has been attributed to the ability of compounds such as 2-PG to inhibit reuptake and/or compete with the active endocannabinoids for access to inactivating enzymes such as FAAH and monoglyceride lipase.2,3 Palmitoyl serinol is a stable analog of 2-PG bearing an amide linkage in place of the labile glyceryl ester. This has the potential to enhance its “entourage” activities as a result of a prolonged in vivo half-life. Palmitoyl serinol is also an analog of C-16 ceramide. Incubation of neuroblastoma cells with palmitoyl serinol causes apoptosis with an IC50 of approximately 80 µM.4,5
1
Ben-Shabat, S., Fride, E., Sheskin, T., et al. An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol35323-31(1998).
2
Dinh, T.P., Freund, T.F., and Piomelli, D. A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chem Phys Lipids121149-158(2002).
3
Fowler, C.J., Jonsson, K., and Tiger, G. Fatty acid amide hydrolase: Biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol62517-526(2001).
4
Bieberich, E., Kawaguchi, T., and Yu, R.K. N-acylated serinol is a novel ceramide mimic inducing apoptosis in neuroblastoma cells. J Biol Chem275177-181(2000).
5
Bieberich, E., Hu, B., Silva, J., et al. Synthesis and characterization of novel ceramide analogs for induction of apoptosis in human cancer cells. Cancer Lett18155-64(2002).
Room temperature
in continental US; may vary elsewhere
SMILES
Copy SMILES to clipboard
CCCCCCCCCCCCCCCC(NC(CO)CO)=O
Background Reading
Fowler, C.J., Jonsson, K., and Tiger, G. Fatty acid amide hydrolase: Biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol62517-526(2001).
Dinh, T.P., Freund, T.F., and Piomelli, D. A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chem Phys Lipids121149-158(2002).
Bieberich, E., Hu, B., Silva, J., et al. Synthesis and characterization of novel ceramide analogs for induction of apoptosis in human cancer cells. Cancer Lett18155-64(2002).
Bieberich, E., Kawaguchi, T., and Yu, R.K. N-acylated serinol is a novel ceramide mimic inducing apoptosis in neuroblastoma cells. J Biol Chem275177-181(2000).
Ben-Shabat, S., Fride, E., Sheskin, T., et al. An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol35323-31(1998).