prostaglandin E2

Prostaglandin E2 (PGE2) 是一种天然激素，参与人体内的各种生理过程，包括平滑肌收缩和放松、调节血管扩张和收缩、调节血压和炎症调节。

CJ-42794 (CJ-042794)是前列腺素受体 EP4的选择性拮抗剂, 抑制[3H]-PGE2与 EP4受体结合的平均 pKi 为8.5, 对 EP4选择性比 EP1, EP2和 EP3高200多倍。

16,16-Dimethyl prostaglandin E2 is an orally active vertebrate Hematopoietic stem cells homeostasis critical regulator. It can act through EP2 EP4 and has an interaction with the Wnt pathway.

Enzymatically-derived prostaglandin E2 (PGE2) is an optically pure compound whereas PGE2 derived from the free radical-catalyzed peroxidation of arachidonate is a racemic mixture. Ent-PGE2 is the opposite enantiomer of PGE2. Significant amounts of racemic PGE2 (rac-PGE2) are generated in vitro and in vivo in settings of oxidative stress via the isoprostane pathway. A proposed mechanism for the formation of rac-PGE2 involves the base catalyzed equilibration from 15-E2t-isoprostane (8-iso-PGE2), generated from the 15-H2t-isoprostane endoperoxide.

1a,1b-dihomo Prostaglandin E2 (PGE2) is a rare polyunsaturated fatty acid first identified in extracts of sheep vesicular gland microsomes, known to contain COX, incubated with adrenic acid . 1a,1b-dihomo PGE2 has also been identified in conditioned media of RAW 264.7 macrophages stimulated with endotoxin and arachidonic acid . This product is thought to be produced by elongation of AA to adrenic acid, which is then metabolized sequentially by COX and PGE synthase.

11β-PGE2 is the C-11 epimer of PGE2. It is a moderate inhibitor of PGE2 binding to rat hypothalamic membranes with a Ki value of 53 nM.[1] 11β-PGE2 also stimulates bone resorption in rats at concentrations of 10-8 to 10-6 M which is similar to PGE2.2 11β-PGE2 inhibits PGE2 binding to the prostaglandin transporter protein with a Ki of 56 nM.[3] .

15(S)-15-methyl PGE2 is a potent, metabolically stable analog of PGE2. It is a potent gastric antisecretory and antiulcer compound. 15(S)-15-methyl PGE2 binds to human myometrium with twice the affinity of PGE2 and is ten times more potent than PGE1 in contracting uterine smooth muscle.

8-iso PGE2 is one of several isoprostanes produced from arachidonic acid during lipid peroxidation. It is a potent renal vasoconstrictor in the rat. 8-iso PGE2 inhibits U-46619 or I-BOP-induced platelet aggregation with IC50 values of 0.5 and 5 μM, respectively. When infused into the renal artery of the rat at a concentration of 4 μg/kg/min, 8-iso PGE2 decreases the GFR and renal plasma flow by 80% without affecting blood pressure.

8-iso PGE2 isopropyl ester is a more lipophilic form of the free acid, 8-iso PGE2. Prostaglandin esters have enhanced lipid solubility compared to their parent compounds. They are generally hydrolyzed to the free acid upon in vivo administration, making the esters useful prodrugs. In general, the C-1 esters of prostaglandins show greatly diminished agonist activity in vitro compared to the parent free acids.

8-iso Prostaglandin E2 (8-iso PGE2) is one of several isoprostanes produced from polyunsaturated fatty acids during lipid peroxidation. 8-iso-16-cyclohexyl-tetranor PGE2 is a synthetic analog of 8-iso PGE2. There are no published studies on the pharmacological properties of 8-iso-16-cyclohexyl-tetranor PGE2.

9-deoxy-9-methylene Prostaglandin E2 (9-deoxy-9-methylene PGE2) is a stable, isosteric analog of PGE2 . 9-deoxy-9-methylene PGE2 retains the biological profile of PGE2 with fewer side effects. In the rat 9-deoxy-9-methylene PGE2 is equipotent to PGE2 in decreasing blood pressure. It also stimulates the gerbil colon and primate uterus at the same potency as PGE2.

9-deoxy-9-methylene-16,16-dimethyl Prostaglandin E2 (Meteneprost) is a potent analog of prostaglandin E2 with an extended half-life in vivo. In combination with various other prostaglandin derivatives, it results in the termination of first trimester pregnancy in monkeys. A single intramuscular injection containing 0.5 mg of meteneprost and 7.5 mg of 17-phenyl trinor PGF1α is very effective in terminating early pregnancy. This prostaglandin mixture is ineffective on monkeys in their third trimester of pregnancy. Meteneprost, when compared to PGE2 and PGF1α, in monkey and rat, does not result in unwanted side effects such as fever or gastrointestinal problems.

20-hydroxy Prostaglandin E2 (20-hydroxy PGE2) is a product of cytochrome P450 metabolism of PGE2 . ω-Oxidation at C-20 followed by β-oxidation and the loss of up to four carbons from the lower side chain is a prominent metabolic pathway for PGE2. 20-hydroxy PGE2 is the putative first intermediate in this chain of chemical transformations.

Prostaglandin E2 (PGE2) isopropyl ester is a more lipophilic form of the free acid, PGE2. PG esters have enhanced lipid solubility compared to their parent compounds. They are generally hydrolyzed to the free acid by endogenous esterases upon in vivo administration, making the esters useful prodrugs. In general, the C-1 esters of PGs show greatly diminished receptor activity in vitro compared to the parent free acids.

17-phenyl trinor PGE2 ethyl amide is derived from 17-phenyl trinor PGE2, a synthetic analog of PGE2 that acts as an agonist of EP1 and EP3 receptors in mice (Ki = 14 and 3.7 nM, respectively) and EP1, EP3, and EP4 in rats (Ki = 25, 4.3, and 54 nM, respectively). 17-phenyl trinor PGE2 causes contraction of guinea pig ileum at a concentration of 11 μM and is 4.4 times more potent than PGE2 as an antifertility agent in hamsters. Modification of the C-1 carboxyl group to an ethyl amide serves to increase lipid solubility, thereby improving uptake into tissues and further lowering the effective concentration. Ethyl amide groups are then removed by amidases, regenerating the active free acid.

11-deoxy Prostaglandin E2 (11-deoxy PGE2) is a stable, synthetic analog of PGE2 . In contrast to PGE2 which has bronchodilation effects, 11-deoxy PGE2 is a powerful bronchoconstrictor and contracts human respiratory tract smooth muscle with potencies ranging from 5 to 30 times higher than PGF2α .

5-trans-Prostaglandin E2 accelerates fibrinolysis by enhancing plasminogen activation mediated by tissue-type plasminogen activator. It also inhibits platelet aggregation in human PRP.

15-keto-Prostaglandin E2为内源性代谢产物，通过与STAT3Cys259残基结合，抑制STAT3激活作用。该化合物能够结合并稳定EP2与EP4受体，进而抑制乳腺癌细胞生长与进展，并通过激活PPAR-γ促进真菌生长。

Prostaglandin E2抑制剂3是一种microsomal prostaglandin E合酶-1 (mPGES-1; IC50 = 0.2 µM)的抑制剂，相较于COX-1、COX-2、5-lipoxygenase (5-LO)和soluble epoxide hydrolase (sEH)，在10 µM的无细胞试验中表现出对mPGES-1的选择性。在10 µM和1 µM的浓度下，该抑制剂能抑制A549细胞中IL-1β诱导的PGE2生成以及在J774A.1巨噬细胞中，LPS诱导的IL-6和PGE2生成。同时，它还能抑制由钙离子载体A23187单独或结合花生四烯酸和A23187诱导的5-LO产物形成，包括白三烯B4 (LTB4) 和5-H(p)ETE（IC50s分别为4.9和5.2 µM）。在体内，10 mg/kg剂量的Prostaglandin E2抑制剂3能防止在zymosan诱导的小鼠腹膜炎模型中白细胞渗入腹腔液中。

Prostaglandin E2 serinol amide 为 [3H]2-油酰甘油水解的弱抑制剂。该化合物无法通过水解产生 PGE2，因此不参与抑制白三烯 B4 的生物合成、超氧化物的生成、迁移以及抗菌肽的释放。

Prostaglandin E2 Ethanolamide (PGE2-EA) 作为PGE2的类似物，通过COX-2催化内源性大麻素进行氧化而形成，具有可能调控人血以及人单核细胞中促炎细胞因子TNF-α产生的功能。

11-Deoxy-16,16-dimethyl Prostaglandin E2 (11-deoxy-16,16-dimethyl PGE2) is a stable synthetic analog of Prostaglandin E2 (PGE2), acting as an agonist for both EP2 and EP3 receptors. It effectively inhibits gastric acid secretion and ulcer formation in rats, with ED50 values of 1 mg kg and 0.021 mg kg, respectively. This compound is also 900 times more potent than Prostaglandin F2α (PGF2α) in inducing contraction of human respiratory tract smooth muscle in vitro.

13,14-dihydro-15-keto Prostaglandin E2 (13,14-dihydro-15-keto PGE2) serves as the predominant metabolite of PGE2 in plasma, created through a 15-keto PGE2 intermediate by the action of 15-oxo-PG Δ13 reductase. Unlike its precursor PGE2, this compound exhibits poor binding affinity towards EP2 and EP4 PGE2 receptors (Ki values of 12 and 57 µM, respectively) in CHO cells and fails to stimulate adenylate cyclase activity therein (EC50s >18 and >38 µM, respectively). Concentrations of 13,14-dihydro-15-keto PGE2 are notably higher in the plasma of pregnant women during their third trimester and at labor and delivery stages, whereas its levels are found to be reduced in the tumor tissues of patients with non-small cell lung cancer (NSCLC) compared to adjacent healthy tissue.

15(R)-Prostaglandin E2, the C-15 epimer of the more physiologically abundant 15(S)-PGE2 (sc-201225) isomer, is produced mainly from arachidonic acid (sc-200770) via the action of COX and PGES enzymes. Present in nearly all cell types, PGE2 interacts with four distinct receptors, EP1 to EP4, leading to a wide range of biological effects. However, 15(R)-Prostaglandin E2 exhibits significantly lower efficacy in most biological assays compared to its 15(S) counterpart. Notably, acid catalyzed epimerization can transform 15(R)-Prostaglandin E2 into the more active 15(S)-Prostaglandin E2 form.