13,14-dihydro-15-keto Prostaglandin E2-d4

13,14-dihydro-15-keto Prostaglandin E2-d4 (13,14-dihydro-15-keto PGE2-d4) is intended for use as an internal standard for the quantification of 13,14-dihydro-15-keto PGE2 (Item No. 14650) by GC- or LC-MS. 13,14-dihydro-15-keto PGE2 is a metabolite of PGE2 (Item No. 14010) and the primary PGE2 metabolite in plasma.1,2 It is formed from PGE2 via a 15-keto PGE2 intermediate by 15-oxo-PG Δ13 reductase.2 Unlike PGE2, 13,14-dihydro-15-keto PGE2 does not bind effectively to the PGE2 receptors EP2 and EP4 expressed in CHO cells (Kis = 12 and 57 µM, respectively) or induce adenylate cyclase activity in the same cells (EC50s = >18 and >38 µM, respectively). Levels of 13,14-dihydro-15-keto PGE2 are increased in the plasma of women in the third trimester of pregnancy and in women during and immediately after labor and delivery.3 Levels of 13,14-dihydro-15-keto PGE2 levels are decreased in tumor tissue compared to adjacent non-cancerous tissue isolated from patients with non-small cell lung cancer (NSCLC).4WARNING This product is not for human or veterinary use.

[1] M. HAMBERG B S. On the Metabolism of Prostaglandins E1 and E2 in Man[J]. Journal of Biological Chemistry, 1971, 246 1: 6713-6721. DOI: 10.1016/s0021-9258(19)45905-x
[2] N. NISHIGAKI A I M Negishi. Two Gs-coupled prostaglandin E receptor subtypes, EP2 and EP4, differ in desensitization and sensitivity to the metabolic inactivation of the agonist.[J]. Molecular Pharmacology, 1996, 146 1: 1031-1037. DOI: 10.1254/fpj.108.supplement_65
[3] P. HUSSLEIN  H. S. Concentration of 13,14-dihydro-15-keto-prostaglandin E2 in the maternal peripheral plasma during labour of spontaneous onset[J]. Bjog-An International Journal of Obstetrics and Gynaecology, 1984, 91 3: 228-231. DOI: 10.1111/j.1471-0528.1984.tb04757.x
[4] DUNCAN HUGHES. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase regulates levels of bioactive lipids in non-small cell lung cancer.[J]. Cancer prevention research (Philadelphia, Pa.), 2008, 1 4: 241-249. DOI: 10.1158/1940-6207.capr-08-0055
[5] DAVID MERIWETHER. Apolipoprotein A-I mimetics mitigate intestinal inflammation in COX2-dependent inflammatory bowel disease model.[J]. Journal of Clinical Investigation, 2019, 129 9: 3670-3685. DOI: 10.1172/jci123700
[6] CHRISTOPHER G. PARKER. Ligand and Target Discovery by Fragment-Based Screening in Human Cells[J]. Cell, 2017, 168 1: 527-541.e29. DOI: 10.1016/j.cell.2016.12.029