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| Targets |
GSK-1521498 targets the μ-opioid receptor (MOR), a G protein-coupled receptor that is the primary target for endogenous opioid peptides and for opioid drugs such as morphine and fentanyl. MOR is a key component of the brain's reward circuitry and is involved in mediating the euphoric and analgesic effects of opioids. GSK-1521498 is a potent and selective antagonist of MOR. By blocking MOR signaling, it attenuates the rewarding effects of drugs of abuse and of palatable foods, thereby reducing compulsive behaviors.
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| ln Vitro |
In vitro, GSK-1521498 is a potent and selective μ-opioid receptor antagonist. Its activity is typically measured using receptor binding assays and functional assays. In receptor binding assays, its affinity (Ki) for the μ-opioid receptor is determined. In functional assays, its ability to inhibit MOR-mediated signaling, such as the inhibition of cAMP accumulation, is measured. However, specific IC50 or Ki values are not detailed in standard product descriptions. The compound's selectivity for MOR over other opioid receptors has been confirmed.
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| ln Vivo |
In vivo, GSK-1521498 has been shown to attenuate reward-driven compulsive behaviors, such as stimulant drug seeking or binge eating, in animal models and humans. It has been investigated for its potential in treating obesity, alcoholism, and drug addiction. By blocking MOR signaling, it reduces the rewarding effects of drugs and food, thereby decreasing compulsive consumption. However, specific in vivo protocols and results, such as efficacy in clinical trials, are not detailed in standard product descriptions.
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| Enzyme Assay |
The in vitro assays for GSK-1521498 measure its binding to and antagonism of the μ-opioid receptor. Receptor binding assays are performed using membranes from cells expressing the MOR and a radiolabeled MOR ligand. GSK-1521498 is added at increasing concentrations to compete with the labeled ligand. The Ki is determined from the competition curve. Functional assays measure the compound's ability to inhibit MOR-mediated signaling. Cells expressing the MOR are treated with a MOR agonist (e.g., DAMGO) in the presence of GSK-1521498, and the inhibition of cAMP accumulation or the activation of G protein-coupled inwardly rectifying potassium channels (GIRKs) is measured.
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| Cell Assay |
In vitro cell-based assays for GSK-1521498 are conducted using cells expressing the human μ-opioid receptor. In a typical assay, cells are seeded in multi-well plates and treated with a MOR agonist to stimulate signaling. GSK-1521498 is added at various concentrations, and the inhibition of agonist-induced effects is measured. For example, the inhibition of cAMP accumulation can be measured using a competitive immunoassay. The IC50 is determined from the dose-response curve. These assays confirm the compound's potent antagonistic activity at the MOR.
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| Animal Protocol |
In vivo animal experiments for GSK-1521498 have been conducted in models of drug addiction and binge eating. In a typical study, animals are trained to self-administer a drug of abuse (e.g., cocaine) or to consume palatable food. GSK-1521498 is administered, and the effects on drug-seeking or food consumption are measured. The compound's ability to reduce these reward-driven behaviors is assessed. These studies confirm that GSK-1521498 attenuates compulsive behaviors.
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| ADME/Pharmacokinetics |
GSK-1521498 has a molecular weight that is not specified in the available literature. It is a solid compound. It is soluble in DMSO and other organic solvents. For storage, it is recommended to keep the powder at -20°C. Detailed pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have been studied in the context of research. However, specific values are not detailed in standard product descriptions. As a research compound, its stability is maintained by proper storage.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for GSK-1521498 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. GSK-1521498 is a selective μ-opioid receptor antagonist, and its toxicity would be related to its effects on MOR-mediated signaling. However, comprehensive toxicological studies have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling GSK-1521498. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References | |
| Additional Infomation |
GSK1521498 has been used in trials investigating the treatment of obesity and alcoholism.
GSK-1521498 is a research compound and is not approved for any clinical or therapeutic use. It is a potent and selective antagonist of the μ-opioid receptor (MOR). It has been shown to attenuate reward-driven compulsive behaviors, such as stimulant drug seeking or binge eating, in animals and humans. It has potential applications in obesity, alcoholism, and drug addiction. Its mechanism of action involves blocking MOR signaling, which is involved in the brain's reward circuitry. GSK-1521498 is a valuable research tool for studying opioid receptor pharmacology and reward mechanisms. |
| Molecular Formula |
C24H20F2N4
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|---|---|
| Molecular Weight |
402.44
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| Exact Mass |
326.134
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| CAS # |
1007573-18-3
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| Related CAS # |
GSK1521498 free base (hydrochloride);1007578-24-6;GSK1521498;1426543-84-1
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| PubChem CID |
24737629
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| Appearance |
White to off-white solid powder
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| LogP |
3.397
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
537
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WIEDUMBCZQRGSY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H20F2N4/c25-22-11-19(15-6-3-7-18(8-15)24-28-14-29-30-24)12-23(26)21(22)13-27-20-9-16-4-1-2-5-17(16)10-20/h1-8,11-12,14,20,27H,9-10,13H2,(H,28,29,30)
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| Chemical Name |
N-[[2,6-difluoro-4-[3-(1H-1,2,4-triazol-5-yl)phenyl]phenyl]methyl]-2,3-dihydro-1H-inden-2-amine
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| Synonyms |
GSK-1521498 GSK 1521498GSK1521498 GSK-1521498B
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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 : ~11.36 mg/mL (~28.23 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4848 mL | 12.4242 mL | 24.8484 mL | |
| 5 mM | 0.4970 mL | 2.4848 mL | 4.9697 mL | |
| 10 mM | 0.2485 mL | 1.2424 mL | 2.4848 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01366573 | COMPLETED | Drug: GSK1521498 Other: Placebo |
Alcoholism | GlaxoSmithKline | 2011-05-13 | Phase 1 |
| NCT00976066 | COMPLETED | Drug: Part A Assessing GSK1521498 Drug: Part B Assessing GSK1521498 Drug: Part C Assessing Naltrexone |
Obesity | GlaxoSmithKline | 2009-06-15 | Phase 1 |
| NCT00976066 | COMPLETED | Drug: Part A Assessing GSK1521498 Drug: Part B Assessing GSK1521498 Drug: Part C Assessing Naltrexone |
Obesity | GlaxoSmithKline | 2009-06-15 | Phase 1 |
| NCT01195792 | COMPLETED | Drug: GSK1521498 Drug: Placebo |
Obesity | GlaxoSmithKline | 2010-09 | Phase 2 |
| NCT00976105 | COMPLETED | Drug: Zolpidem or placebo - Hypnotic drug given for sleep disorders Drug: GSK1521498 or placebo |
Obesity | GlaxoSmithKline | 2009-09-22 | Phase 1 |
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