PGE2-G.Prostaglandin E2 glyceryl ester

PGE2-G illustrates where the endocannabinoid system meets the prostaglandin pathway: when cyclooxygenase-2 is induced, it oxygenates 2-arachidonoylglycerol as effectively as arachidonic acid and so diverts part of the cannabinoid signal into prostanoid chemistry (Kozak 2000). The molecule has a pharmacology of its own: in RAW264.7 macrophages it mobilises calcium, raises inositol trisphosphate and activates protein kinase C and then ERK1/2, where PGE2 itself does not mobilise calcium, and these responses do not depend on its hydrolysis (Nirodi 2004). In 2017 the nucleotide receptor P2Y6 was identified as its specific target, with an EC50 of about 1 pM against about 50 nM for its natural ligand UDP (Brüser 2017). In rodents, PGE2-G is endogenously present, its levels fall under COX-2 inhibition, and intraplantar administration causes mechanical allodynia and thermal hyperalgesia; a cocktail of prostanoid receptor antagonists only partially abolishes these effects, which led the authors to speak of an « enzymatic switch » by which COX-2 converts antinociceptive 2-AG into a pro-nociceptive prostanoid (Hu 2008). In isolated human neutrophils, by contrast, the inhibitory effect observed requires hydrolysis into PGE2 and goes through the EP2 receptor (Turcotte 2017). Human in vivo data are lacking: there is no clinical trial, no descriptive pharmacology in humans, and no therapeutic benefit is established.

Source

An endogenous mammalian metabolite, absent from hemp: the molecule does not form in the Cannabis sativa plant but in animal cells, when cyclooxygenase-2 oxygenates 2-arachidonoylglycerol, the body's most abundant endocannabinoid. Its production was observed in cultured macrophages (Kozak 2000) and its endogenous presence established in the rat, where levels fall under inhibition of COX-2 as well as of monoacylglycerol lipase, and are unaffected by carrageenan-induced inflammation (Hu 2008).

2-arachidonoylglycerol, released from membrane phospholipids by diacylglycerol lipase, serves as a substrate for cyclooxygenase-2, which oxygenates it into the glyceryl endoperoxide PGH2-G; prostaglandin synthases then convert this intermediate, cellular PGD synthase for instance affording PGD2-G in macrophages. This production from endogenous 2-AG stores is calcium-dependent and mediated by diacylglycerol lipase and COX-2 (Kozak 2000). In the rat, COX-2 inhibition lowers tissue levels of PGE2-G (Hu 2008).

European Union

No member state schedules this molecule as a narcotic. It appears neither in the schedules of the 1961 and 1971 United Nations conventions nor in the EUDA early warning system, and it has never been critically reviewed by the WHO expert committee. No authorisation is granted to it under the novel food regulation. Its use remains confined to biomedical research.

France

An endogenous metabolite, not listed on the French narcotics and psychotropics lists (orders of 22 February 1990). PGE2-G does not belong to the benzo[c]chromene family covered by the ANSM decisions of June 2024 and is not a tetrahydrocannabinol. Continuously produced by the body, it physically circulates only as a laboratory reagent and analytical standard, outside any authorised food or cosmetic use.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Family

Endocannabinoid or related mediator › Endocannabinoidome

Verification

Every fact on this entry was checked against its primary sources on 20 October 2026.

Wikipedia (English)

No dedicated article.

1. 1Kozak, Rowlinson & Marnett 2000, J Biol Chem: oxygenation of 2-arachidonoylglycerol to glyceryl prostaglandins by COX-2 (new tab)PMID 10931854
2. 2Nirodi et al. 2004, PNAS: the glyceryl ester of PGE2 mobilises calcium and activates signal transduction in RAW264.7 cells (new tab)PMID 14766978
3. 3Hu et al. 2008, Br J Pharmacol: PGE2-G, an endogenous COX-2 metabolite of 2-AG, induces hyperalgesia and alters NF-κB activity (new tab)PMID 18297109
4. 4Brüser et al. 2017, Sci Rep: PGE2-G is an endogenous agonist of the nucleotide receptor P2Y6 (EC50 ≈ 1 pM) (new tab)PMID 28539604
5. 5Turcotte et al. 2017, J Immunol: PGE2-G inhibits human neutrophil functions after hydrolysis to PGE2, via EP2 (new tab)PMID 28258202
6. 6Scheaffer et al. 2020, ACS Omega: role of CES1 in the catabolism of prostaglandin glyceryl esters (new tab)PMID 33225149
7. 7PubChem CID 24778489, 1(3)-glyceryl-PGE2 (new tab)

SMILES

CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1C/C=C\CCCC(=O)OCC(CO)O)O)O

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