Sulprostone (SHB 286) is a specific EP3 receptor agonist. Sulprostone (SHB 286) is a prostaglandin E2 (PGE2) analog with antiulcer and non-steroidal anti-abortive effects. Sulprostone may be utilized in termination of pregnancy and bleeding during childbirth.

Physicochemical Properties

Molecular Formula	C23H31NO7S
Molecular Weight	465.56
Exact Mass	465.182
Elemental Analysis	C, 59.34; H, 6.71; N, 3.01; O, 24.06; S, 6.89
CAS #	60325-46-4
Related CAS #	96420-78-9 (unknown MF)
PubChem CID	5312153
Appearance	Colorless to light yellow liquids
Density	1.3±0.1 g/cm3
Melting Point	78.5-80ºC
Index of Refraction	1.589
LogP	0.26
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	12
Heavy Atom Count	32
Complexity	766
Defined Atom Stereocenter Count	4
SMILES	CS(=O)(NC(CCC/C=C\C[C@@H]1[C@H]([C@H](O)CC1=O)/C=C/[C@@H](O)COC2=CC=CC=C2)=O)=O
InChi Key	UQZVCDCIMBLVNR-TWYODKAFSA-N
InChi Code	InChI=1S/C23H31NO7S/c1-32(29,30)24-23(28)12-8-3-2-7-11-19-20(22(27)15-21(19)26)14-13-17(25)16-31-18-9-5-4-6-10-18/h2,4-7,9-10,13-14,17,19-20,22,25,27H,3,8,11-12,15-16H2,1H3,(H,24,28)/b7-2-,14-13+/t17-,19-,20-,22-/m1/s1
Chemical Name	(Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-5-oxocyclopentyl]-N-methylsulfonylhept-5-enamide
Synonyms	Sulprostone; SHB-286; C60325-46-4; Nalador; CP-34089; ZK-57671; CP-34,089; ZK 57 671; 501Q5EQ1GM; SHB 286; CP34089; ZK57671
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	EP3
ln Vitro	Sulprostone (SHB 286) has Ki values of 21 nM and 0.6 nM for EP1 and EP3 in cultivated Chinese hamster ovary cells[1]. Sulprostone (1, 1.5 or 2 mg/mL) does not significantly change the vitality and the purity of Dendritic cells (DCs). Sulprostone hinders spontaneous and directed DC migration independently from its concentration. Sulprostone reduces the expression of CCR7 and impairs migration of DCs[2].
ln Vivo	AUC of 149 ng·h/mL, Vss of 0.583 L/kg, CL of 56 mL/min·kg, and T1/2 of 0.451 hours are all observed in sulprostone (SHB 286; 0.5 mg/kg; IV)[3].
Enzyme Assay	Sulprostone is a potent prostaglandin E2 (PGE2) analogue and one of the first identified selective G-protein-coupled receptor 3 (EP3) agonists. It has been investigated as a potential antiulcer agent and frequently used in the research of EP3 antagonist. To assist pharmacokinetic and pharmacodynamic studies, a rapid and sensitive LC-MS/MS method was developed and qualified for the quantitation of sulprostone in monkey plasma. Using electrospray ionization mass spectrometry, an ammonium adduct in positive mode was chosen for analysis which had seven times of the sensitivity of the depronated ion in negative mode. Latanoprost, a prostaglandin F2α analogue, was used as the internal standard while good sensitivity and chromatography were obtained on a 2.6 μm core-shell column with pentafluorophenyl stationary phase. An assay dynamic range of 2 to 4000 ng/mL was achieved with a sample volume of 25 μL plasma on a Sciex API4000 instrument with simple protein precipitation. Several esterase inhibitors including sodium fluoride (NaF), phenylmethanesulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP), paraoxon and dichlorvos as well as wet ice conditions were explored for the stabilization of sulprostone in monkey plasma. The developed method was successfully applied for the evaluation of pharmacokinetics of sulprostone after intravenous administration of 0.5 mg/kg to cynomolgus monkey[3].
Cell Assay	We evaluated the feasibility of dinoprostone (PGE2) replacement with the molecular analog sulprostone, in our good manufacturing practice (GMP) protocol for the generation of DC-based cancer vaccine. We characterized the phenotype and the function of DCs matured in the presence of sulprostone as a potential substitute of dinoprostone in the pro-inflammatory maturation cocktail consisting of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6. Results: We found that sulprostone invariably reduces the recovery, but does not significantly modify the viability and the purity of DCs. The presence of sulprostone in the maturation cocktail increases the adhesion of single cells and of clusters of DCs to the flask, making them more similar to their immature counterpart in terms of adhesion and spreading proprieties. Moreover, we observed that sulprostone impairs the expression of co-stimulatory molecules and the spontaneous as well as the directed migration capacity of DCs.[2]
Animal Protocol	Animal/Disease Models: Male cynomolgus monkey[3] Doses: 0.5 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: IV Experimental Results: Had a T1/2 of 0.451 hrs (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]. Prostanoid receptors: structures, properties, and functions. Physiol Rev. 1999 Oct;79(4):1193-226. [2]. Skewing effect of sulprostone on dendritic cell maturation compared with dinoprostone. Cytotherapy. 2018 Jun;20(6):851-860. [3]. 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.
Additional Infomation	Sulprostone is a prostanoid. Sulprostone has been used in trials studying Abortion, Induced.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1480 mL	10.7398 mL	21.4795 mL
	5 mM	0.4296 mL	2.1480 mL	4.2959 mL
	10 mM	0.2148 mL	1.0740 mL	2.1480 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.