pge2 production

Rebamipide (OPC12759) is a quinolinone derivative with anti-ulcer and anti-inflammatory activities. Rebamipide induces cyclooxygenase 2 (COX2) synthesis which results in an increase in endogenous prostaglandin synthesis in the gastric mucosa. This agent also inhibits H. pylori-induced production of tumor necrosis factor (TNF) alpha and subsequent inflammation of the gastric mucosa. In addition, rebamipide scavenges oxygen-derived free radicals that potentially cause mucosal injury, and stimulates prostaglandin EP4 receptor gene expression followed by mucous secretion, thereby enhancing the gastric mucosal defense.

1. Flavokawain B (Flavokavain B) has potent anti-inflammatory activity, can significantly inhibit production of NO and PGE2 in LPS-induced RAW 264.7 cells. 2. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK NF-κB and MAPK signaling pathways. 3. Flavokawain B induces apoptosis, has the potential usefulness of FKB for prevention and treatment of hormone-refractory prostate cancer in an adjuvant setting. 4. Flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells.

mPGES1-IN-4 (compound 32) is a multi-substituted pyrimidine compound acting as a submicromolar inhibitor of PGE2 production. It primarily exerts its anti-inflammatory effects by inhibiting mPGES-1 and significantly suppresses acute inflammation models in vivo.

mPGES1-IN-5 (compound 18) is a multi-substituted pyrimidine compound that acts as a submicromolar inhibitor of PGE2 production. It primarily exerts its anti-inflammatory effects by inhibiting mPGES-1 and demonstrates significant inhibitory activity in vivo against acute inflammation models.

AGU654 (Compound 44) is a selective mPGES-1 inhibitor with an IC50 value of 2.9 nM against mPGES-1. By inhibiting mPGES-1, AGU654 interrupts the pathway where COX-1 2 converts arachidonic acid to prostaglandin E2 (PGE2), effectively reducing inflammatory responses, pain, and fever symptoms. In models using activated human monocyte-derived macrophages and whole blood, AGU654 selectively inhibits PGE2 production induced by bacterial endotoxins, while preserving the production of other prostaglandins. In guinea pig models, AGU654 significantly alleviates fever, inflammation, and inflammatory pain, demonstrating excellent anti-inflammatory, analgesic, and antipyretic effects. AGU654 holds promise as a new approach for researching inflammatory diseases and pain.

DBMB is a spleen tyrosine kinase (Syk) inhibitor that significantly suppresses Syk enzyme activity. It possesses anti-inflammatory properties by inhibiting NF-κB signaling, thereby reducing the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2). DBMB can be utilized in research on inflammatory diseases.

YS121 is a dual inhibitor of microsomal prostaglandin E2 synthase-1 (mPGES-1; IC50=3.4 μM) and 5-lipoxygenase (5-LOX; IC50=6.5 μM). YS121 dose-dependently reduces the production of PGE2 with EC50=12 μM in IL-1β-stimulated A549 cells [1].

TCS 2510 (CAY10598) is a selective PGE2 and EP4 receptor agonist that enhances the intracellular concentration of cAMP and the abundance of active β-caten.TCS 2510 inhibits TNF-alpha production and may be useful in the study of diseases associated with metabolic disorders.

CAY10526 (BTH) is a selective mPGES-1 inhibitor that acts as an inhibitor of the NF-κB signaling pathway.

Dehydroevodiamine (DHED), a constituent of Evodia rutaecarpa, has various biological effects such as hypotensive, negative chronotropic, ion channel depressant, inhibition of nitric oxide production and cerebral blood flow enhancing activities.

2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005). 2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2 References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005).

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). Pyrrophenone inhibits cPLA2α with an IC50 of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE2 and LTC4 in cells (IC50 = 24, 25, and 14 nM, respectively). Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA2s with more than a hundred-fold less potency. Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-stimulated AA release from monocytic cells, interleukin-1-induced PGE2 synthesis in mesangial cells, and the production of PGE2, LTs, and platelet-activating factor by human neutrophils, always with maximal inhibition at concentrations below 1 μM.

CAFESTOL is a ERK inhibitor for AP-1-targeted activity against PGE2 production and the mRNA expression of cyclooxygenase (COX)-2 in LPS-activated RAW264.7 cells. Cafestol has strong inhibitory activity on PGE2 production by suppressing the NF-kB activation pathway.

7-Demethylsuberosin (7-demethylsuberosin) is a coumarin compound isolated from Angelica gigas Nakai,and has anti-inflammatory activity,and exhibited inhibitory effects on PGE2 production with the IC50 values of 9.42 μM.

1. Isofraxidin (Phytodolor) protects leukemia cells from radiation-induced apoptosis via ROS mitochondria pathway in a p53-independent manner. 2. Isofraxidin has a protective effect against LPS-induced ALI, and the protective effect of Isofraxidin seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2. 3. Isofraxidin possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1 2.

1. alpha-Cyperone (α-Cyperone) is a promising inhibitor of Hla production by S. aureus and protects lung cells from this bacterium. 2. alpha-Cyperone significantly inhibited PGE2 production by suppressing the LPS-induced expression of inducible COX-2 at both the mRNA and the protein levels , downregulated the production and mRNA expression of the inflammatory cytokine IL-6. 3. alpha-Cyperone inhibited actin cytoskeleton polymerization induced by APEC-O78 through down regulating the expression of Nck-2, Cdc42 and Rac1.

iNOS PGE2-IN-1 is an iNOS PGE2 inhibitor and a potent anti-inflammatory agent. iNOS PGE2-IN-1 exhibits an inhibitory effect on LPS-induced NO production and has a low ulcerogenic potential.

IKKβ-IN-1 is a potent, orally active inhibitor of IkappaB (IKK-β) with an IC50 of 0.20 μM. It reduces the inhibition of PGE2 and TNF-α production in murine macrophages and protects mice from infection shock-induced death.

COX-2-IN-10 is a potent COX-2 inhibitor that exhibits inhibitory effects on the production of IL-6, TNF-α, and IL-1β, and inhibits PGE2 production in a concentration-dependent manner with an IC50 value of 2.54 μM. Additionally, COX-2-IN-10 inhibits the expression of iNOS and COX-2 at both mRNA and protein levels.

CR6086 is a novel, potent EP4 antagonist showing favourable immunomodulatory properties, striking DMARD effects in rodents, and anti-inflammatory activity targeted to immune-mediated inflammatory diseases and distinct from the general effects of cyclooxygenase inhibitors. CR6086 showed selectivity and high affinity for the human EP4 receptor (Ki = 16.6 nM) and functioned as a pure antagonist (half-maximal inhibitory concentration, 22 nM) on PGE2-stimulated cAMP production.

UT-11 is a potent brain-permeable inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1), exhibiting IC50 values of 0.10 μM and 2.00 μM for the inhibition of PGE2 production in human (SK-N-AS) and murine (BV2) cells, respectively [1].

Prostaglandin E2 (PGE2) inhibitor 3 is a selective inhibitor targeting microsomal prostaglandin E synthase-1 (mPGES-1; IC50 = 0.2 µM), demonstrating greater selectivity for mPGES-1 over COX-1, COX-2, 5-lipoxygenase (5-LO), and soluble epoxide hydrolase (sEH) in assays at 10 µM. This compound effectively reduces IL-1β-induced PGE2 production in A549 cells and decreases LPS-induced IL-6 and PGE2 in J774A.1 macrophages at concentrations of 10 and 1 µM, respectively. Additionally, it blocks the production of 5-LO-derived products, including leukotriene B4 (LTB4) and 5-H(p)ETE, in response to calcium ionophore A23187 alone or combined with arachidonic acid, with IC50 values of 4.9 and 5.2 µM, respectively. When administered in vivo at doses of 10 mg/kg, PGE2 inhibitor 3 effectively prevents leukocyte infiltration in a mouse model of zymosan-induced peritonitis.

2-Chloroadenosine-5'-O-diphosphate, a purine nucleotide adenosine 5'diphosphate (ADP) derivative, demonstrates multiple biological activities. It promotes aggregation and inhibits cyclic AMP (cAMP) production, triggered by prostaglandin E2 (PGE2), in a concentration-dependent manner within isolated human platelet-rich plasma. Additionally, this compound facilitates the relaxation of precontracted isolated guinea pig taenia coli strips (pD2 = 6.74) and reduces arterial blood pressure in rats. Moreover, 2-Chloroadenosine-5'-O-diphosphate significantly inhibits the ATPase activity of mortalin, a member of the heat shock protein 70 (Hsp70) family, with an apparent Ki of 45.05 µM for the human enzyme.

Prostaglandin E2 Serinol Amide acts as a weak inhibitor against the hydrolysis of [3H]2-oleoylglycerol, but it is non-hydrolyzable and cannot produce PGE2. Consequently, it is unable to inhibit leukotriene B4 biosynthesis, superoxide production, migration, and the release of antimicrobial peptides [1].