PGE2 x PGES

Last update 08 May 2025

Basic Info

Related Targets

PGE2PGES

Drugs associated with PGE2 x PGES

EP4023638

Patent Mining

Target

PGE2 x PGES

Mechanism-

Active Org.

KUKJE PHARMA Co., Ltd.

Originator Org.

KUKJE PHARMA Co., Ltd.

Active Indication

Arthritis [+3]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PGE2 x PGES

100 Translational Medicine associated with PGE2 x PGES

0 Patents (Medical) associated with PGE2 x PGES

639

Literatures (Medical) associated with PGE2 x PGES

01 May 2025·Journal of Molecular Graphics and Modelling

Discovery of novel microsomal prostaglandin E2 synthase 1 (mPGES-1) inhibitors by a structurally inspired virtual screening study

Article

Author: Kretzer, Christian ; Olğaç, Abdurrahman ; Banoglu, Erden ; Jordan, Paul M ; Werz, Oliver

Prostaglandin (PG) E₂ is a pro-inflammatory lipid mediator derived from the metabolism of arachidonic acid (AA) by cyclooxygenases (COX) and PGE₂ synthases. Nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used in the treatment of inflammation, nonselectively inhibit COX activity and decrease PGE₂ production. However, these drugs cause gastrointestinal bleeding and several cardiovascular complications. Therefore, inhibiting microsomal PGE₂ Synthase-1 (mPGES-1) to block PGE₂ production downstream of COX is expected to yield safer and more effective treatments for inflammation, cancer, and cardiovascular diseases. At present, there are no mPGES-1 inhibitors available on the market, but ongoing research continuously evaluates new compounds in both preclinical and clinical stages. Here, we conducted a high throughput virtual screening campaign to discover novel mPGES-1 inhibitor scaffolds. This campaign utilized physicochemical filtering alongside both structure-aware ligand-based approaches (shape screening templates and pharmacophore models, which were generated based on the 3D binding modes of the co-crystallized mPGES-1 inhibitors) and structure-based strategies (refinement with docking and molecular dynamics). Thirty-four compounds were selected and biologically tested for mPGES-1 inhibition in a cell-free assay using microsomes from interleukin-1β-stimulated A549 cells as the source of mPGES-1. The most potent compound inhibited the remaining enzyme activity with an IC₅₀ value of 6.46 μM in a cell-free assay for PGE₂ production. We also compared the binding patterns of the most active compounds identified in this study with those of co-crystallized inhibitors using molecular dynamics simulations. This comparison underscored the crucial role of ionic interactions, π-π interactions, hydrogen bonds, and water bridges involving specific amino acids. Our results highlight the importance of these interaction networks within the binding cavity in various binding scenarios. Ultimately, the insights gained from this study could assist in designing and developing new mPGES-1 inhibitors.

01 Apr 2025·Cancer Letters

LIN28B enhances the chemosensitivity of colon cancer cells via inducing genomic instability by upsetting the balance between the production and removal of reactive oxygen species

Article

Author: Li, Yanping ; Hu, Shijie ; Li, Guoli ; Hu, Ziyi ; Li, Kai ; Wu, Di ; Wang, Guangyu ; Wang, Tianzhen ; Li, Muhan ; Liang, Zhigang ; Weng, Mingjiao ; Yu, Fei ; Li, Xiaobo

Genomic instability is an enabling characteristic that allows cancer cells to acquire additional hallmarks of cancer through the accumulation of alterations in driver genes. Furthermore, it creates opportunities to enhance the sensitivity of cancer cells to chemotherapeutic agents targeting DNA, owing to the presence of incomplete DNA damage repair pathways. This study identifies LIN28B as a crucial regulator of colon cancer cells' sensitivity to DNA damage- or repair-related compounds by promoting genomic instability. LIN28B mechanistically reduces glutathione (GSH) synthesis and activity by inhibiting the expression of four GSH metabolic enzymes (GCLC, G6PD, GSTM4, and GSTT2B), thereby reducing the capacity of cells to eliminate reactive oxygen species (ROS). LIN28B enhances the proinflammatory signaling pathway in cancer cells through the upregulation of ARID3A, a transcription factor that transactivates PTGES and PTGES2, resulting in increased production of PGE2, a key inflammatory mediator that can elevate ROS generation. In conclusion, LIN28B altered the equilibrium of ROS production and elimination in colon cancer, resulting in elevated ROS levels and subsequent genomic instability.

14 Mar 2025·Reproduction

Placental interleukin 1β signaling in canine pregnancy: differential effects during and after decidualization in vitro

Article

Author: Tavares Pereira, Miguel ; Payan-Carreira, Rita ; Reynaud, Karine ; Kowalewski, Mariusz P ; Aslan, Selim ; Reichler, Iris M

In briefThe role of inflammation in the regulation of pregnancy remains poorly understood in dogs. Findings from this study propose the involvement of IL1β signaling during early embryo-maternal interactions in the dog, while in vitro effects suggest it may disrupt decidual cell function in the canine mature placenta.AbstractAlthough implantation and parturition are associated with pro-inflammatory signals, inflammatory responses in the mature placenta frequently lead to pregnancy loss. Indeed, uterine inflammatory/infectious diseases are major causes of infertility and pregnancy loss in dogs. The pro-inflammatory interleukin (IL)-1β is increased during canine placentation and downregulated in mature placentae during healthy pregnancies but is enriched in the placenta during infectious events. Furthermore, canine pregnancy success is linked with decidual cells, the only placental cells expressing the nuclear progesterone receptor. This study assessed utero-placental abundance of IL1β receptor 1 (IL1R1) throughout canine pregnancy and possible modulatory effects of IL1β on decidualization. The mRNA levels of IL1R1 were increased in mature mid-gestation placentae and at term (P < 0.05). Immunohistochemistry co-localized IL1β and IL1R1 in the trophoblast during early placentation, implicating IL1β-signaling in early embryo-maternal communication. In the mature placenta, IL1R1 was localized, i.a. in decidual cells. In vitro, IL1β had low modulatory effects on PGE2- and/or P4-stimulated dog uterine stromal (DUS) cells, implying a relatively weak impact of this interleukin in the decidualization process. However, in DUS cells decidualized with cAMP, IL1β decreased transcriptional amounts of selected decidualization markers IGF1, PTGS2 and PTGES, as well as ECM1 and TIMP2 (P < 0.001). Transcriptional and protein availabilities of CX43, a gap junction component, were also decreased by IL1β (P < 0.001). These findings support a dual role for IL1β in canine pregnancy: involvement in early embryo-maternal communication during its establishment and disturbing placental homeostasis by disrupting decidual cell function in fully developed placenta.

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