Description
15-keto Prostaglandin E
2 (15-keto PGE
2) is a metabolite of PGE
2 (Item Nos.
14010) formed by 15-hydroxy prostaglandin dehydrogenase (15-PGDH). Unlike PGE
2, 15-keto PGE
2 does not bind effectively to the PGE
2 receptors EP
2 and EP
4 expressed in CHO cells (K
is = 2.6 and 15 μM, respectively) or induce adenylate cyclase activity in the same cells (EC
50s = 1.8 and >33 μM, respectively). However, it does bind to EP
2 and EP
4 in HEK cells expressing these receptors (IC
50s = 0.117 and 2.82 μM, respectively), as well as induces cAMP formation (EC
50s = 0.137 and 0.426 μM, respectively) and the transcriptional activity of β-catenin/TCF in the same cells. 15-keto PGE
2 inhibits CD3-CD28-MHC-I-induced proliferation of isolated human CD4
+ T cells in a concentration-dependent manner. It also reduces mortality in a mouse model of LPS-induced sepsis when administered at a dose of 15 mg/kg.
15-keto PGE
2 MaxSpec
® standard is a quantitative grade standard of 15-keto PGE
2 that has been prepared specifically for mass spectrometry or any application where quantitative reproducibility is required. The solution has been prepared gravimetrically and is supplied in a deactivated glass ampule sealed under argon. The concentration was verified by comparison to an independently prepared calibration standard. This 15-keto PGE
2 MaxSpec
® standard is guaranteed to meet identity, purity, stability, and concentration specifications and is provided with a batch-specific certificate of analysis. Ongoing stability testing is performed to ensure the concentration remains accurate throughout the shelf life of the product.
Note: The amount of solution added to the vial is in excess of the listed amount. Therefore, it is necessary to accurately measure volumes for preparation of calibration standards. Follow recommended storage and handling conditions to maintain product quality.
Uses
15-keto Prostaglandin E2 (15-keto PGE2) is a metabolite of PGE2 formed by 15-hydroxy PGDH. 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).[Cayman Chemical]
References
[1] 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[2] SUZU ENDO. 15-Keto-PGE2 acts as a biased/partial agonist to terminate PGE2-evoked signaling.[J]. The Journal of Biological Chemistry, 2020: 13338-13352. DOI:
10.1074/jbc.ra120.013988[3] LISA SCHMIDLEITHNER. Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction.[J]. Immunity, 2019: 1232-1248.e14. DOI:
10.1016/j.immuni.2019.03.014[4] ING-JUNG CHEN . Targeting the 15-keto-PGE2-PTGR2 axis modulates systemic inflammation and survival in experimental sepsis[J]. Free Radical Biology and Medicine, 2018, 115: Pages 113-126. DOI:
10.1016/j.freeradbiomed.2017.11.016[5] CARLOS ARTéRIO SORGI. Comprehensive high-resolution multiple-reaction monitoring mass spectrometry for targeted eicosanoid assays[J]. Scientific Data, 2018, 5 1: 1-12. DOI:
10.1038/sdata.2018.167[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
