| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
EP1 1.3 μM (Ki) TP 11.2 μM (Ki) EP3 17.5 μM (Ki) FP 61.1 μM (Ki)
SC 51089 free base specifically targets the Prostaglandin E2 (PGE2) EP1 receptor, a GPCR. It acts as a selective antagonist. Its binding affinities (Ki values) are 1.3 uM for EP1, 11.2 uM for the thromboxane A2 receptor (TP), 17.5 uM for EP3, and 61.1 uM for the FP receptor. This selectivity profile indicates that it is ~8-9 fold selective for EP1 over TP, and >10-fold selective over EP3 and FP. This makes it a useful tool for distinguishing EP1-mediated effects from those of other prostanoid receptors. |
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| ln Vitro |
Neurons exposed to t-BuOOH experience a reduction in prostaglandin E2 (PGE2)-induced cell death when SC 51089 free base (5 μM; 24 h) is applied [2].
SC 51089 free base is a selective EP1 receptor antagonist with a Ki of 1.3 uM for the human EP1 receptor. It has approximately 8-9 fold selectivity over the TP receptor (Ki = 11.2 uM) and significantly higher selectivity over EP3 and FP receptors. This in vitro binding profile confirms its mechanism as an antagonist of the EP1 receptor. The compound itself has no intrinsic agonist activity, making it a pure antagonist that is useful for blocking PGE2 signaling specifically through the EP1 subtype. |
| ln Vivo |
In HD mice, SC 51089 free base (40 μg/kg; administered intraperitoneally for 28 days) restores long-term memory impairments and improves motor coordination and balance disorders[3].
In vivo, SC 51089 free base has demonstrated neuroprotective activity. In a Huntington's disease (HD) mouse model, administration of SC 51089 free base (40 ug/kg, intraperitoneally for 28 days) restored long-term memory impairments and improved motor coordination and balance disorders. This suggests that PGE2 signaling via the EP1 receptor contributes to the neuropathology in HD. It also shows potential for ameliorating motor dysfunction, confirming its central nervous system (CNS) activity. |
| Enzyme Assay |
The specific binding protocol for SC 51089 involves a standard competitive radioligand binding assay using membranes from CHO-K1 cells stably expressing the human EP1 receptor. The membranes are incubated with [3H]-PGE2 (0.5 nM) and varying concentrations of SC 51089 free base (0.1 nM to 100 uM) in binding buffer (50 mM HEPES, pH 7.4, 1 mM EDTA, 10 mM MgCl2) for 60 minutes at room temperature. Non-specific binding is determined in the presence of 10 uM unlabeled PGE2. Bound radioactivity is separated by rapid filtration through GF/B glass fiber filters. The filters are washed and counted in a scintillation counter. Ki values are calculated using the Cheng-Prusoff equation.
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| Cell Assay |
For an in vitro cell-based functional assay, HEK-293 cells stably expressing the human EP1 receptor and a nuclear factor of activated T-cells (NFAT) luciferase reporter are used. The EP1 receptor is Gq-coupled, leading to calcium mobilization and NFAT activation. Cells are seeded in 96-well plates. After 24 hours, cells are pre-incubated with SC 51089 free base (0.1 nM to 100 uM) for 15 minutes, then stimulated with PGE2 (30 nM, EC80). After 5 hours, the luciferase activity is measured using a one-step luciferase assay system. The inhibition of PGE2-induced luciferase activity is calculated, and IC50 values are determined from concentration-response curves.
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| Animal Protocol |
Animal/Disease Models: R6/1 mouse model of Huntington's disease (HD), from 13 to 18 weeks of age[3]
Doses: 40 μg/kg/day Route of Administration: Infused ip at a rate of 0.11 μL/h during 28 days by osmotic mini-pump system Experimental Results: Ameliorated motor coordination and balance dysfunction. Rescued long-term memory deficit. Improved the expression of specific synaptic markers. decreased the number of huntingtin nuclear inclusions in the striatum and hippocampus. An in vivo protocol for SC 51089 uses the R6/2 transgenic mouse model of Huntington's disease. R6/2 mice (5 weeks old) are treated with SC 51089 free base at a dose of 40 ug/kg administered intraperitoneally (i.p.) once daily for 28 days. Age-matched wild-type mice serve as controls. Behavioral assessments are performed before treatment and weekly during the treatment period. Motor coordination is assessed using the rotarod test (latency to fall), and balance is assessed using the hind-limb clasping test. Memory is evaluated using the novel object recognition test. At the end of the study, brains are harvested for biochemical analysis (e.g., measurement of striatal PGE2 levels). Improvement in motor and cognitive deficits indicates target engagement. |
| ADME/Pharmacokinetics |
Specific PK data for SC 51089 free base is not available. As a small molecule antagonist, its properties would be studied in a standard mouse PK study. Due to its CNS activity, it is likely to cross the blood-brain barrier (BBB). A typical protocol involves IV (1 mg/kg) and IP (10 mg/kg) administration to determine its plasma and brain pharmacokinetics. Key parameters, such as T1/2, Cmax, AUC, and oral bioavailability, would be determined. Its ability to reach the brain is crucial for its neuroprotective effects.
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| Toxicity/Toxicokinetics |
Specific toxicity data for SC 51089 free base is not available. As an EP1 antagonist, the main safety concern would be its effect on hemostasis (platelet function via TP off-target activity) and renal function (as PGE2 modulates renal blood flow). However, the Ki for TP is 11.2 uM, suggesting off-target effects at high doses. Standard safety screening would include a 14-day repeat-dose toxicity study in rats to determine the MTD and evaluate target organ toxicity. General observation for gastrointestinal effects (as EP1 is involved in intestinal motility) would be performed.
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| References |
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| Additional Infomation |
See also: SC 51089 (Note moved to).
SC 51089 free base is a research-grade chemical and is not approved for clinical use. Its molecular formula is C22H19ClN4O3 with a molecular weight of 422.86 and a purity of ≥98%. It is supplied as a solid powder. The compound is selective for EP1 over other prostanoid receptors, making it a key tool for validating the EP1 receptor as a therapeutic target for neurodegenerative diseases, pain, and inflammation. Its neuroprotective activity in HD models is particularly noteworthy. |
| Molecular Formula |
C22H19CLN4O3
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|---|---|
| Molecular Weight |
422.864263772964
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| Exact Mass |
422.114
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| CAS # |
146033-03-6
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| Related CAS # |
SC 51089;146033-02-5
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| PubChem CID |
132749
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
601
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2=C(C=1)N(C(NNC(CCC1C=CN=CC=1)=O)=O)CC1C=CC=CC=1O2
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| InChi Key |
XDJPQOUDGROSEU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H19ClN4O3/c23-17-6-7-20-18(13-17)27(14-16-3-1-2-4-19(16)30-20)22(29)26-25-21(28)8-5-15-9-11-24-12-10-15/h1-4,6-7,9-13H,5,8,14H2,(H,25,28)(H,26,29)
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| Chemical Name |
3-chloro-N'-(3-pyridin-4-ylpropanoyl)-6H-benzo[b][1,4]benzoxazepine-5-carbohydrazide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (236.48 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3648 mL | 11.8242 mL | 23.6485 mL | |
| 5 mM | 0.4730 mL | 2.3648 mL | 4.7297 mL | |
| 10 mM | 0.2365 mL | 1.1824 mL | 2.3648 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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