15-keto Prostaglandin E2 (15-keto PGE2) is a metabolite of PGE2 formed by 15-hydroxy PGDH. [1] [2] In vivo, 15-keto PGE2 is essentially inactive. It has an attenuated affinity for the EP4 and EP2 receptors compared to PGE2 (Ki = 2,600-15,000 nM for the inhibition of PGE2 binding compared to a Kd = 1 nM for PGE2).[3]
Reference:
[1]. Hamberg, M., and Samuelsson, B. On the metabolism of prostaglandins E1 and E2 in man. J. Biol. Chem. 246(22), 6713-6721 (1971).
[2]. Mak, O.T., Liu, Y., and Tai, H.H. Purification and characterization of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase from porcine kidney. Biochim. Biophys. Acta 1035(2), 190-196 (1990).
[3]. Nishigaki, N., Negishi, M., and Ichikawa, A. Two Gs-coupled prostaglandin E receptor subtypes, EP2 and EP4, differ in desensitization and sensitivity to the metabolic inactivation of the agonist. Mol. Pharmacol. 50(4), 1031-1037 (1996).