16,16-dimethyl PGE2 is a competitive inhibitor of 15-hydroxy PGDH, but it is not a substrate for the enzyme. Because of its resistance to metabolism by 15-hydroxy PGDH, it has a prolonged half-life in vivo. 16,16-dimethyl PGE2 acts as an agonist on most EP receptor subtypes, and has been used experimentally to induce cervical ripening, uterine contraction, and prevent ulceration of the gastric mucosa in rats and dogs. The Kd for activation of isolated EP2 receptors is about 1 nM. 16,16-dimethyl PGE2 can be used to preserve the self-renewal properties while preventing the differentiation of hematopoietic stem cells during expansion in culture.
ChEBI: 16,16-dimethylprostaglandin E2 is a prostanoid that is prostaglandin E2 in which both of the hydrogens at position 16 have been replaced by methyl groups. A synthetic analogue of prostaglandin E2, it is a potent inhibitor of pancreatic function and growth of experimental tumors. It also protects the gastric mucosa, prevents ulceration, and promotes the healing of peptic ulcers. It has a role as a radiation protective agent, an anti-ulcer drug and a gastrointestinal drug. It is a prostanoid, a monocarboxylic acid, a secondary allylic alcohol and a member of cyclopentanones.
dmpge2 was reported to cause an increase in runx11/cmyb1 hscs, while hscs were inhibited by indomethacin treatment in 90% of embryos. moreover, dmpge2 had minimal effects on the vasculature, while indomethacin altered the intersomitic vessels slightly. imaged by confocal microscopy, red-labelled hscs and endothelium embryos showed significantly increased hscs following dmpge2 exposure [1].
in a heterotopic model of rat allograft rejection, dmpge2 could delay the rejection onset, but all animals developed severe rejection and died subsequently. treatment of animals with low-dose csa in combination with dmpge2 led to a delay in the onset as well as a reduction in the intensity of allograft rejection. in addition, a statistical relationship between procoagulant activity levels and the time of onset of rejection was observed [1].
[1] north te,goessling w,walkley cr,lengerke c,kopani kr,lord am,weber gj,bowman tv,jang ih,grosser t,fitzgerald ga,daley gq,orkin sh,zon li. prostaglandin e2 regulates vertebrate haematopoietic stem cell homeostasis. nature.2007 jun 21;447(7147):1007-11.
[2] koh ih,kim pc,chung sw,waddell t,wong py,gorczynski r,levy ga,cohen z. the effects of 16, 16 dimethyl prostaglandin e2 therapy alone and in combination with low-dose cyclosporine on rat small intestinal transplantation. transplantation.1992 oct;54(4):592-8.
