| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GSK‑269984A targets the EP1 receptor, one of four PGE2 receptors involved in pain and inflammation. As a competitive antagonist, it blocks PGE2‑induced signalling, reducing nociception. It has pA2 of 8.1 and Schild slope of 1.0, confirming competitive mechanism.
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| ln Vitro |
GSK-269984A has a pIC50 of 7.9 and is an antagonist of the EP1 receptor, according to the [3H]-PGE2 binding experiment conducted in CHO cells overexpressing the human EP1 receptor. The PGE2 dose-response curve was observed to move to the right in a concentration-dependent manner when GSK-269984A was added. Schild analysis revealed that GSK-269984A is a competitive antagonist with a pA2 of 8.1±0.3 and a slope of 1.0 [1].
In vitro, GSK‑269984A causes concentration‑dependent rightward shift of PGE2 dose‑response curve, with pIC50 7.9. Schild analysis gives pA2 8.1, confirming competitive antagonism. It shows good potency in cell‑based calcium mobilisation assays using EP1‑expressing cells. |
| ln Vivo |
The oral ED50 of GSK-269984A is 2.6 mg/kg, and the hypersensitivity reversal observed at the 10 mg/kg dose was similar to that of the standard. According to the half-lives in each species, GSK-269984A demonstrated moderate blood clearance in dogs and rats and high clearance in monkeys [1].
In vivo, GSK‑269984A demonstrates analgesic efficacy with oral ED50 of ~2.6 mg/kg in rodent inflammatory pain models (e.g., formalin test, carrageenan paw oedema). However, high clearance in primates prevented further clinical development, limiting its translational potential. |
| Enzyme Assay |
EP1 binding affinity is determined by radioligand displacement using [³H]PGE2 and membrane preparations from EP1‑expressing cells; non‑specific binding is defined with excess PGE2, and Ki is calculated from competition curves.
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| Cell Assay |
Cell‑based assays use CHO cells expressing human EP1; cells are loaded with calcium dye and stimulated with PGE2 in the presence of GSK‑269984A; inhibition of calcium flux is measured to assess antagonism.
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| Animal Protocol |
In vivo rodent pain models: oral administration of GSK‑269984A; pain response is measured by formalin‑induced licking or paw oedema; ED50 is determined. PK/PD studies assess exposure‑response relationships.
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| ADME/Pharmacokinetics |
GSK‑269984A showed moderate PK stability in preclinical species but high clearance in primates, limiting its clinical utility. Oral bioavailability is likely, but rapid metabolism or excretion in primates hindered development.
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| Toxicity/Toxicokinetics |
No detailed toxicity data are reported; however, its development was stopped due to PK issues rather than toxicity. Safety profile in preclinical species may have been acceptable, but high clearance prevented adequate exposure.
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| References | |
| Additional Infomation |
GSK‑269984A is a research compound; its EP1 antagonism provides a tool for studying PGE2‑mediated pain. Although not clinically developed, it contributed to understanding EP1 pharmacology and the challenges of developing EP1 antagonists for pain.
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| Molecular Formula |
C20H13NO3FCL2-.NA+
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|---|---|
| Molecular Weight |
428.21632
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| Exact Mass |
427.015
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| CAS # |
892664-04-9
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| Related CAS # |
892664-17-4 (GSK-269984B)
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| PubChem CID |
23696973
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| Appearance |
White to off-white solid powder
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| LogP |
4.06
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
504
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ROPHIKMBWGQPQO-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C20H14Cl2FNO3.Na/c21-14-6-7-19(27-11-12-4-5-15(22)10-17(12)23)13(8-14)9-16-2-1-3-18(24-16)20(25)26;/h1-8,10H,9,11H2,(H,25,26);/q;+1/p-1
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| Chemical Name |
2-Pyridinecarboxylic acid, 6-((5-chloro-2-((4-chloro-2-fluorophenyl)methoxy)phenyl)methyl)-, sodium salt
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| Synonyms |
GSK-269984A; GSK269984A; GSK 269984A
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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 |
| 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 : ~7 mg/mL (~16.31 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 | 2.3352 mL | 11.6762 mL | 23.3525 mL | |
| 5 mM | 0.4670 mL | 2.3352 mL | 4.6705 mL | |
| 10 mM | 0.2335 mL | 1.1676 mL | 2.3352 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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