Prostaglandin E2
[CAS# 363-24-6]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Prostaglandins
• Name: Prostaglandin E2
• Synonyms: Dinoprostone; (5Z,11a,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid; 7-[3-Hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-5-heptenoic acid; PGE2
• Molecular Formula: C₂₀H₃₂O₅
• Molecular Weight: 352.47
• CAS Registry Number: 363-24-6
• EC Number: 206-656-6
• SMILES: CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1C/C=CCCCC(=O)O)O)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Melting point: 66 °C (Expl.)
• Boiling point: 530.1±50.0 °C 760 mmHg (Calc.)^*
• Flash point: 288.5±26.6 °C (Calc.)^*
• Solubility: water insoluble, DMSO (100mM), ethanol (45mM) (Expl.)
• Index of refraction: 1.561 (Calc.)^*
• Alpha: -85.5 ° (c=1, C2H5OH) (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302-H360
• Safety Statements: P203-P264-P270-P280-P301+P317-P318-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Repr.	2	H360
Reproductive toxicity	Repr.	1A	H360
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Prostaglandin E₂ (PGE₂) is a naturally occurring eicosanoid derived from arachidonic acid through the cyclooxygenase (COX) pathway. It was first identified in human seminal plasma in the 1930s and subsequently characterized as a prostaglandin with potent biological activity in multiple tissues. PGE₂ is synthesized by the sequential action of COX enzymes, which convert arachidonic acid to the unstable intermediate prostaglandin H₂ (PGH₂), followed by PGE synthases that catalyze the formation of PGE₂. PGE₂ functions as a local autocrine and paracrine signaling molecule due to its rapid metabolism and short half-life.

PGE₂ exerts its effects through binding to four distinct G protein-coupled receptors, designated EP1, EP2, EP3, and EP4, each of which mediates different intracellular signaling pathways. EP1 typically activates phospholipase C and increases intracellular calcium, EP2 and EP4 activate adenylate cyclase to raise cyclic AMP levels, and EP3 couples to multiple G proteins to produce inhibitory or stimulatory effects depending on the tissue context. The tissue-specific distribution of these receptors explains the diverse physiological and pathophysiological roles of PGE₂.

Physiologically, PGE₂ regulates vascular tone, gastrointestinal integrity, renal function, bone remodeling, and reproductive processes. In the gastrointestinal tract, it maintains mucosal protection by stimulating mucus and bicarbonate secretion and promoting mucosal blood flow. In the kidneys, it modulates glomerular filtration and sodium excretion. PGE₂ also plays a critical role in inflammation and fever, mediating vasodilation, increasing vascular permeability, and acting on the hypothalamus to induce pyrexia. Furthermore, PGE₂ is involved in labor induction by promoting cervical ripening and uterine contractions, which has led to its clinical application as a labor-inducing agent.

The clinical applications of PGE₂ include the induction of labor, termination of pregnancy, treatment of gastric ulcers, and the management of patent ductus arteriosus in neonates. Synthetic analogs and stable derivatives have been developed to enhance stability, receptor selectivity, and therapeutic efficacy. Misoprostol, a methyl ester analog of PGE₁, and dinoprostone, the pharmacologically active form of PGE₂, are examples used in obstetrics and gynecology to induce labor or as abortifacients. These derivatives exploit the receptor-mediated actions of PGE₂ while improving pharmacokinetic properties such as oral bioavailability and metabolic stability.

Research on PGE₂ has also highlighted its involvement in pathological conditions, including cancer, chronic inflammation, and cardiovascular diseases. Overexpression of COX-2 and elevated PGE₂ levels are associated with tumorigenesis, angiogenesis, and immune modulation in cancer. PGE₂ contributes to inflammatory disorders such as rheumatoid arthritis by promoting synovial inflammation and pain. These findings have spurred the development of COX inhibitors and EP receptor modulators as therapeutic strategies to regulate PGE₂ signaling in disease.

References

Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294 1871–1875 DOI: 10.1126/science.294.5548.1871

Ricciotti E, FitzGerald GA (2011) Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology 31 986–1000 DOI: 10.1161/ATVBAHA.110.207449

Regan JW (2003) EP2 and EP4 prostanoid receptor signaling. Life Sciences 74 143–153 DOI: 10.1016/j.lfs.2003.09.031