Sulprostone

Names

[ Name ]:
Sulprostone

[Synonym ]:
Sulprostonum
N-Acetyl-N-acetoxy-4-chlorobenzenesulfonamide
Nalador
[1R-[1a(Z),2b(1E,3R*),3a]]-7-[3-Hydroxy-2-(3-hydroxy-4-phenoxy-1-butenyl)-5-oxocyclopentyl]-N-(methylsulfonyl)-5-heptenamide
Sulprostone
SHB-286
Sulprostona
(5Z)-7-{(1R,2R,3R)-3-Hydroxy-2-[(1E,3R)-3-hydroxy-4-phenoxybut-1-en-1-yl]-5-oxocyclopentyl}-N-(methylsulfonyl)hept-5-enamide
(5Z)-7-{(1R,2R,3R)-3-Hydroxy-2-[(1E,3R)-3-hydroxy-4-phenoxy-1-buten-1-yl]-5-oxocyclopentyl}-N-(methylsulfonyl)-5-heptenamide
5-Heptenamide, 7-[(1R,2R,3R)-3-hydroxy-2-[(1E,3R)-3-hydroxy-4-phenoxy-1-buten-1-yl]-5-oxocyclopentyl]-N-(methylsulfonyl)-, (5Z)-
SHB 286
EINECS 262-173-0

Biological Activity

[Description]:

Sulprostone (SHB 286), a prostaglandin E2 (PGE2) analogue, is a potent and selective EP3 receptor agonist. Sulprostone has potential antiulcer and nonsteroidal abortifacient effects used for the research of pregnancy termination and hemorrhages during delivery[1][2][3].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Prostaglandin Receptor

Research Areas >> Inflammation/Immunology

[Target]

EP3 Receptor

[In Vitro]

Sulprostone (SHB 286) has Ki values of 21 nM and 0.6 nM for EP1 and EP3 in cultured Chinese hamster ovary cells[1]. Sulprostone (1, 1.5 or 2 mg/mL) does not significantly modify the viability and the purity of Dendritic cells (DCs). Sulprostone impairs spontaneous and directed DC migration independently from its concentration. Sulprostone reduces the expression of CCR7 and impairs migration of DCs[2].

[In Vivo]

Sulprostone (0.5 mg/kg; IV) has a T1/2 of 0.451 hours, a CL of 56 mL/min•kg, a Vss of 0.583 L/kg and an AUC of 149 ng•h/mL[3]. Animal Model: Male cynomolgus monkey[3] Dosage: 0.5 mg/kg (Pharmacokinetic Analysis) Administration: IV Result: Had a T1/2 of 0.451 hours, a CL of 56 mL/min•kg, a Vss of 0.583 L/kg and an AUC of 149 ng•h/mL.

[References]

[1]. S Narumiya, et al. Prostanoid receptors: structures, properties, and functions. Physiol Rev. 1999 Oct;79(4):1193-226.

[2]. Jenny Bulgarelli, et al. Skewing effect of sulprostone on dendritic cell maturation compared with dinoprostone. Cytotherapy. 2018 Jun;20(6):851-860.

[3]. Yifan Shi, et al. Bioanalysis of sulprostone, a prostaglandin E 2 analogue and selective EP 3 agonist, in monkey plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Aug 15;1092:51-57.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Melting Point ]:
78.5-80ºC

[ Molecular Formula ]:
C₂₃H₃₁NO₇S

[ Molecular Weight ]:
465.560

[ Exact Mass ]:
465.182129

[ PSA ]:
138.38000

[ LogP ]:
0.26

[ Index of Refraction ]:
1.589

[ Storage condition ]:
−20°C

[ Water Solubility ]:
DMSO: >5 mg/mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MJ8810000

CHEMICAL NAME :: 5-Heptenamide, 7-(3-hydroxy-2-(3-hydroxy-4-phenoxy-1-butenyl)-5-oxoc yclopentyl)- N-(methylsulfonyl)-, (1R-(1-alpha(Z),2-beta(1E,3R*),3-alpha))-

CAS REGISTRY NUMBER :: 60325-46-4

LAST UPDATED :: 199803

DATA ITEMS CITED :: 14

MOLECULAR FORMULA :: C23-H31-N-O7-S

MOLECULAR WEIGHT :: 465.61

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 12 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EKFAE9 Eksperimental'naya i Klinicheskaya Farmakologiya. Experimental and Clinical Pharmacology. (Mezhdunarodnaya Kniga, ul. B. Yakimanka, 39, 117049 Moscow, Russia) V.55- 1992- Volume(issue)/page/year: 56(4),37,1993

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 18 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EKFAE9 Eksperimental'naya i Klinicheskaya Farmakologiya. Experimental and Clinical Pharmacology. (Mezhdunarodnaya Kniga, ul. B. Yakimanka, 39, 117049 Moscow, Russia) V.55- 1992- Volume(issue)/page/year: 56(4),37,1993

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 3 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EKFAE9 Eksperimental'naya i Klinicheskaya Farmakologiya. Experimental and Clinical Pharmacology. (Mezhdunarodnaya Kniga, ul. B. Yakimanka, 39, 117049 Moscow, Russia) V.55- 1992- Volume(issue)/page/year: 56(4),37,1993 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 17 ug/kg

SEX/DURATION :: female 23 week(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 137,8,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 10 ug/kg

SEX/DURATION :: female 9 week(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 19,29,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 20 ug/kg

SEX/DURATION :: female 49 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 22,471,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 30 ug/kg

SEX/DURATION :: female 15 week(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 26,279,1982

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 15 ug/kg

SEX/DURATION :: female 7 week(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Fertility - abortion

REFERENCE :: GOBIDS Gynecologic and Obstetric Investigation. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.9- 1978- Volume(issue)/page/year: 29,10,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 5 ug/kg

SEX/DURATION :: female 10 week(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 27,51,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraplacental

DOSE :: 500 ng/kg

SEX/DURATION :: female 15 week(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 26,279,1982

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intracervical

DOSE :: 1 ug/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 16,377,1977

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 550 mg/kg

SEX/DURATION :: female 6-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: EKFAE9 Eksperimental'naya i Klinicheskaya Farmakologiya. Experimental and Clinical Pharmacology. (Mezhdunarodnaya Kniga, ul. B. Yakimanka, 39, 117049 Moscow, Russia) V.55- 1992- Volume(issue)/page/year: 56(4),37,1993

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 900 ug/kg

SEX/DURATION :: female 21-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: 44LQAF "International Sulprostone Symposium, Papers, Vienna, 1978," Friebel, K., et al., eds., Berlin, Fed. Rep. Ger., Schering AG, 1979 Volume(issue)/page/year: -,39,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 120 ug/kg

SEX/DURATION :: female 63-64 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

REFERENCE :: ACEDAB Acta Endocrinologica, Supplementum (Copenhagen). (Periodica, Skolegade 12 E, DK-2500 Valby, Denmark) No.1- 1948- Volume(issue)/page/year: 253,148,1983

Safety Information

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H315-H319-H335-H360

[ Precautionary Statements ]:
P201-P261-P305 + P351 + P338-P308 + P313

[ Personal Protective Equipment ]:
Eyeshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ Hazard Codes ]:
T:Toxic

[ Risk Phrases ]:
R60;R36/37/38

[ Safety Phrases ]:
53-22-36/37-45

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
MJ8810000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Quantitative phosphoproteomic analysis of signaling downstream of the prostaglandin e2/g-protein coupled receptor in human synovial fibroblasts: potential antifibrotic networks.

J. Proteome Res. 13(11) , 5262-80, (2014)

The Prostaglandin E2 (PGE2) signaling mechanism within fibroblasts is of growing interest as it has been shown to prevent numerous fibrotic features of fibroblast activation with limited evidence of d...

Angiogenesis in the primate ovulatory follicle is stimulated by luteinizing hormone via prostaglandin E2.

Biol. Reprod. 92(1) , 15, (2015)

Rapid angiogenesis occurs as the ovulatory follicle is transformed into the corpus luteum. To determine if luteinizing hormone (LH)-stimulated prostaglandin E2 (PGE2) regulates angiogenesis in the ovu...

PGE2 reduces MMP-14 and increases plasminogen activator inhibitor-1 in cardiac fibroblasts.

Prostaglandins Other Lipid Mediat. 113-115 , 62-8, (2014)

Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the mem...