363-24-6 Usage
Description
Prostaglandin E2 (PGE2) is an endogenous prostaglandin derived from the action of cyclooxygenase on arachidonic acid. It is the most common and most biologically potent of mammalian prostaglandins, with diverse biological actions in areas such as inflammation, cancer, immune modulation, fertility, smooth muscle relaxation, and hematopoietic stem cell homeostasis. PGE2 acts through four distinct receptors: EP1, EP2, EP3, and EP4. It is a white to pale yellowish-cream powder and is known for its oxytocic and abortifacient properties.
Uses
Used in Pharmaceutical Applications:
Prostaglandin E2 is used as an abortifacient and oxytocic agent for inducing cervical ripening and labor. It is administered in a single dose of 10 mg by controlled-release (0.3 mg/hr) vaginal insert, potentiating the effects of oxytocin. Brand names include Cervidil, Prepidil, Prostin E2, Minprostin, Prostaglandin, Prostarmon E, and Prostin VR Pediatric.
Used in Cell Culture Applications:
PGE2 is utilized in cell culture applications for the study of prostaglandin-regulated cell signaling and gene regulation, aiding in understanding its diverse biological actions and potential therapeutic applications.
Used in Research and Development:
Prostaglandin E2 is used in research and development for studying its role in various biological processes, including inflammation, cancer, immune modulation, fertility, and smooth muscle relaxation. This helps in the development of targeted therapies and understanding the underlying mechanisms of action for PGE2.
Originator
Prostin E2,Upjohn,UK,1972
Manufacturing Process
Hexamethyldisilazane (1 ml) and trimethylchlorosilane (0.2 ml) are added
with stirring to a solution of PGA2 (250 mg) in 4 ml of tetrahydrofuran at 0°C
under nitrogen. This mixture is maintained at 5°C for 15 hours. The mixture is
then evaporated under reduced pressure. Toluene is added and evaporated
twice. Then the residue is dissolved in 6 ml of methanol, and the solution is
cooled to -20°C. Hydrogen peroxide (0.45 ml; 30% aqueous) is added. Then,
1N sodium hydroxide solution (0.9 ml) is added dropwise with stirring at -
20°C. After 2 hours at -20°C, an additional 0.3 ml of the sodium hydroxide
solution is added with stirring at -20°C. After another hour in the range -10°C
to -20°C, an additional 0.1 ml of the sodium hydroxide solution is added.
Then, 1.5 ml of 1 N hydrochloric acid is added, and the mixture is evaporated
under reduced pressure. The residue is extracted with ethyl acetate, and the
extract is washed successively with 1 N hydrochloric acid and ine, dried with
anhydrous sodium sulfate and evaporated. The residue is dissolved in 5 ml of
diethyl ether. To this solution is added 0.5 ml of methanol and 0.1 ml of water.
Amalgamated aluminum made from 0.5 g of aluminum metal is then added in
small portions during 3 hours at 25°C. Then, ethyl acetate and 3 N
hydrochloric acid are added, and the ethyl acetate layer is separated and
washed successively with 1 N hydrochloric acid and ine, dried with
anhydrous sodium sulfate, and evaporated. The residue is chromatographed
on 50 g of acid-washed silica gel, eluting first with 400 ml of a gradient of 50-
100% ethyl acetate in Skellysolve B, and then with 100 ml of 5% methanol in
ethyl acetate, collecting 25 ml fractions. Fractions 9 and 10 are combined and
evaporated to give 18 mg of 11β-PGE2. Fractions 17-25 are combined and
evaporated to give 39 mg of PGE2.
Therapeutic Function
Oxytocic, Abortifacient
World Health Organization (WHO)
Dinoprostone, prostaglandin E2, was introduced into medicine in
1971 and is primarily used for cervical ripening during the induction of labour. It is
available in various formulations for oral, parenteral and vaginal administration.
Tablets, ampoules and vaginal dosage forms (tablets, pessaries, gel) remain
registered in many countries.
Biological Activity
Endogenous prostaglandin and primary product of arachidonic acid/cyclooxygenase pathway. Binds with high affinity to EP 1 , EP 2 , EP 3 and EP 4 receptors (K d values range between ~ 1-10 nM). Influences a wide range of processes including inflammation, smooth muscle relaxation, fertility and gastric mucosal integrity. Regulates vertebrate hematopoietic stem cell (HSC) homeostasis.
Biochem/physiol Actions
Most biologically active prostaglandin. PGE2 induces cervical ripening and parturition; mediates bradykinin-induced vasodilation; regulates adenylyl cyclase. Tumor cells that over-express cyclooxygenase 2 display increased invasiveness, angiogenesis, and resistance to apoptosis that may be due to the PGE2-induced expression of angiogenic factors and stabilization of the anti-apoptotic protein, survivin.The effect of PGE2 on the immune system is mixed. It inhibits T cell activation in vitro, suggesting it is an immunosuppressant. However, in vivo, it appears to effect expansion of the Th17 subset and differentiation of the Th1 subset of T helper cells, marking it as an immunoactivator.
Safety Profile
Poison by
subcutaneous and intravenous routes.
Moderately toxic by ingestion and
intraperitoneal routes. An experimental
teratogen. Human reproductive effects by
intravenous, intraplacental, and intravaginal
routes: changes in the uterus, cervix and
vagina; termination of pregnancy; and
changes in ferthty. Experimental
reproductive effects. Mutation data
reported. When heated to decomposition it
emits acrid smoke and irritating fumes.
in vitro
pge2 can stimulate the gastric nonparietal secretion [3] and has been shown to regulate the function of many cell types including dendritic cells, macrophages, t and b lymphocytes leading to both pro- and anti-inflammatory effects [2].
in vivo
pge2 regulates many physiological systems including the gastrointestinal and immune systems. in the gastrointestinal tract, pge2 plays a protective role in maintaining the integrity of the gastric mucosa. pge2 has also been shown to play a role in the maintenance of blood pressure, particularly in the setting of salt overload [2].
References
1) Healy (1990) Progesterone receptor antagonist and prostaglandins in human fertility regulation: a clinical review; Reprod. Fertil. Dev. 2 477
2) Greenhough et al. (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment; Carcinogenesis, 30 377
3) Kalinski (2012) Regulation of Immune Responses by Prostaglandin E2; J. Immunol., 188 21
4) North et al. (2007) Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis; Nature, 447 1007
5) Hoggatt et al. (2013) Differential stem- and progenitor-cell trafficking by prostaglandin E2; Nature, 495 365
6) Coleman et al. (1994) Classification of prostanoid receptors: Properties, distribution and structure of the receptors and their subtypes; Pharmacol. Rev. 46 205
Check Digit Verification of cas no
The CAS Registry Mumber 363-24-6 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 3,6 and 3 respectively; the second part has 2 digits, 2 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 363-24:
(5*3)+(4*6)+(3*3)+(2*2)+(1*4)=56
56 % 10 = 6
So 363-24-6 is a valid CAS Registry Number.
InChI:InChI=1/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-17,19,21,23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/p-1/b7-4-,13-12+/t15-,16+,17+,19+/m0/s1
363-24-6Relevant articles and documents
A NEW SYNTHETIC ROUTE TO PROSTAGLANDINS
Corey, E. J.,Niimura, Koichi,Konishi, Yoshitaka,Hashimoto, Shinsuke,Hamada, Yasumasa
, p. 2199 - 2202 (1986)
A short synthetic route to prostaglandins is described which depends on oxime-based methodology and which involves the joining of intermediates 9, 11, and 12 in a one-flask operation.
Total synthesis of prostaglandins F2-alpha and E2 as the naturally occurring forms.
Corey,Schaaf,Huber,Koelliker,Weinshenker
, p. 397 - 398 (1970)
-
Schneider
, p. 304 (1969)
Inhibition of cyclooxygenase and prostaglandin E2 synthesis by γ-mangostin, a xanthone derivative in mangosteen, in C6 rat glioma cells
Nakatani, Keigo,Nakahata, Norimichi,Arakawa, Tsutomu,Yasuda, Hideyuki,Ohizumi, Yasushi
, p. 73 - 79 (2002)
The fruit hull of mangosteen, Garcinia mangostana L., has been used for many years as a medicine for treatment of skin infection, wounds, and diarrhea in Southeast Asia. In the present study, we examined the effect of γ-mangostin, a tetraoxygenated diprenylated xanthone contained in mangosteen, on arachidonic acid (AA) cascade in C6 rat glioma cells. γ-Mangostin had a potent inhibitory activity of prostaglandin E2 (PGE2) release induced by A23187, a Ca2+ ionophore. The inhibition was concentration-dependent, with the IC50 value of about 5 μM. γ-Mangostin had no inhibitory effect on A23187-induced phosphorylation of p42/p44 extracellular signal regulated kinase/mitogen-activated protein kinase or on the liberation of [14C]-AA from the cells labeled with [14C]-AA. However, γ-mangostin concentration-dependently inhibited the conversion of AA to PGE2 in microsomal preparations, showing its possible inhibition of cyclooxygenase (COX). In enzyme assay in vitro, γ-mangostin inhibited the activities of both constitutive COX (COX-1) and inducible COX (COX-2) in a concentration-dependent manner, with the IC50 values of about 0.8 and 2 μM, respectively. Lineweaver-Burk plot analysis indicated that γ-mangostin competitively inhibited the activities of both COX-1 and -2. This study is a first demonstration that γ-mangostin, a xanthone derivative, directly inhibits COX activity.
Characterization of aldo-keto reductase 1C subfamily members encoded in two rat genes (akr1c19 and RGD1564865). Relationship to 9-hydroxyprostaglandin dehydrogenase
Satoshi Endo,Matsunaga, Toshiyuki,Hara, Akira
, (2021/02/02)
Rat genes, akr1c19 and RGD1564865, encode members (R1C19 and 20HSDL, respectively) of the aldo-keto reductase (AKR) 1C subfamily, whose functions, however, remain unknown. Here, we show that recombinant R1C19 and 20HSDL exhibit NAD+-dependent dehydrogenase activity for prostaglandins (PGs) with 9α-hydroxy group (PGF2α, its 13,14-dihydro- and 15-keto derivatives, 9α,11β-PGF2 and PGD2). 20HSDL oxidized the PGs with much lower Km (0.3–14 μM) and higher kcat/Km values (0.064–2.6 min?1μM?1) than those of R1C19. They also differed in other properties: R1C19, but not 20HSDL, oxidized some 17β-hydroxysteroids (5β-androstane-3α,17β-diol and 5β-androstan-17β-ol-3-one). 20HSDL was specifically inhibited by zomepirac, but not by R1C19-selective inhibitors (hexestrol, flavonoids, ibuprofen and flufenamic acid), although the two enzymes were sensitive to indomethacin and cis-unsaturated fatty acids. The mRNA for 20HSDL was expressed abundantly in rat kidney and at low levels in the liver, testis, brain, heart and colon, in contrast to ubiquitous expression of R1C19 mRNA. The comparison of enzymic features of R1C19 and 20HSDL with rat PG dehydrogenases and other AKRs suggests not only a close relationship of 20HSDL with 9-hydroxy-PG dehydrogenase in rat kidney, but also roles of R1C19 and rat AKRs (1C16 and 1C24) in the metabolism of PGF2α, PGD2 and 9α,11β-PGF2 in other tissues.
METHOD OF MAKING A CROSS METATHESIS PRODUCT
-
Paragraph 00122; 00123; 00124; 00125, (2019/02/06)
Method of making a cross metathesis product, the method comprising at least step (X) or step (Y): (X) reacting in a cross metathesis reaction a first compound comprising a terminal olefinic group with a second compound comprising a terminal olefinic group, wherein the first and the second compound may be identical or may be different from one another; or (Y) reacting in a ring-closing metathesis reaction two terminal olefinic groups which are comprised in a third compound; wherein the reacting in step (X) or step (Y) is performed in the presence of a ruthenium carbene complex comprising a [Ru=C]-moiety and an internal olefin.
In Situ Methylene Capping: A General Strategy for Efficient Stereoretentive Catalytic Olefin Metathesis. the Concept, Methodological Implications, and Applications to Synthesis of Biologically Active Compounds
Xu, Chaofan,Shen, Xiao,Hoveyda, Amir H.
, p. 10919 - 10928 (2017/08/15)
In situ methylene capping is introduced as a practical and broadly applicable strategy that can expand the scope of catalyst-controlled stereoselective olefin metathesis considerably. By incorporation of commercially available Z-butene together with robust and readily accessible Ru-based dithiolate catalysts developed in these laboratories, a large variety of transformations can be made to proceed with terminal alkenes, without the need for a priori synthesis of a stereochemically defined disubstituted olefin. Reactions thus proceed with significantly higher efficiency and Z selectivity as compared to when other Ru-, Mo-, or W-based complexes are utilized. Cross-metathesis with olefins that contain a carboxylic acid, an aldehyde, an allylic alcohol, an aryl olefin, an α substituent, or amino acid residues was carried out to generate the desired products in 47-88% yield and 90:10 to >98:2 Z:E selectivity. Transformations were equally efficient and stereoselective with a ～70:30 Z-:E-butene mixture, which is a byproduct of crude oil cracking. The in situ methylene capping strategy was used with the same Ru catechothiolate complex (no catalyst modification necessary) to perform ring-closing metathesis reactions, generating 14- to 21-membered ring macrocyclic alkenes in 40-70% yield and 96:4-98:2 Z:E selectivity; here too, reactions were more efficient and Z-selective than when the other catalyst classes are employed. The utility of the approach is highlighted by applications to efficient and stereoselective syntheses of several biologically active molecules. This includes a platelet aggregate inhibitor and two members of the prostaglandin family of compounds by catalytic cross-metathesis reactions, and a strained 14-membered ring stapled peptide by means of macrocyclic ring-closing metathesis. The approach presented herein is likely to have a notable effect on broadening the scope of olefin metathesis, as the stability of methylidene complexes is a generally debilitating issue with all types of catalyst systems. Illustrative examples of kinetically controlled E-selective cross-metathesis and macrocyclic ring-closing reactions, where E-butene serves as the methylene capping agent, are provided.
