| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
pKi: DRD3[1][2].
Dopamine D3 receptor (DRD3). GSK598809 is a competitive and selective antagonist for the DRD3, with greater than 100-fold selectivity over other dopamine receptor subtypes (D1, D2, D4, D5) and a broad panel of other CNS targets including serotonin and muscarinic receptors. |
|---|---|
| ln Vitro |
In non-cellular assays, functional characterization demonstrated that GSK598809 has greater than 100-fold selectivity for dopamine D3 over D2 receptors. In PET imaging studies using the D3-preferring radioligand [11C]PHNO, GSK598809 dose-dependently reduced [11C]PHNO binding in the substantia nigra to near non-specific levels (fPHNOD3 ≈ 100%), confirming its high potency and selectivity for D3 receptors.
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| ln Vivo |
Both GSK598809 and cocaine raise the peak mean arterial blood pressure. In comparison to its vehicle, there are significant differences in the least square means for both cocaine doses. In comparison to its carrier, the least square mean differences for both GSK598809 dosages are substantial. A previous it test on the means of the fitted regression model investigates the experimental topic of interest, which is whether GSK598809 significantly increases cocaine effects on peak mean arterial blood pressure. The pressor effects of 5.6 mg/kg and 1.7 mg/kg cocaine are markedly enhanced by a dosage of 3 mg/kg GSK598809[1].
In vivo, GSK598809 (60 mg p.o.) has been used in human PET imaging studies to determine the relative contributions of D2 and D3 receptors to the [11C]PHNO signal. In rodent models, GSK598809 dose-dependently decreases the expression of nicotine-induced conditioned place preference (CPP), indicating its potential to reduce drug-seeking behavior and craving. |
| Enzyme Assay |
The non-cellular protocol involves a standard competitive radioligand binding assay using human recombinant dopamine receptors expressed in HEK-293 or CHO cell membranes. Membranes are incubated with [3H]methylspiperone or [125I]iodosulpride and varying concentrations of GSK598809 in assay buffer for 60 min at room temperature. Nonspecific binding is determined with 10 uM haloperidol.
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| Cell Assay |
Cell-based assays are not typical for characterizing D3 antagonists like GSK598809. However, functional activity can be assessed using a cAMP accumulation assay in cells co-expressing DRD3 and a chimeric G-protein to couple to adenylyl cyclase. Cells are pre-treated with forskolin, then incubated with varying concentrations of GSK598809, and intracellular cAMP is measured by HTRF.
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| Animal Protocol |
No standard in vivo animal protocol for GSK598809 is provided. For receptor occupancy studies, a typical protocol involves administering GSK598809 orally to rats, followed by injection of a D3-preferring radioligand. After radioligand circulation, animals are euthanized, brain regions dissected, and radioactivity counted. Receptor occupancy is calculated by comparing to vehicle-treated controls.
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| ADME/Pharmacokinetics |
GSK598809 has good physicochemical and pharmacokinetic properties, as it is brain-penetrant and orally bioavailable. In human PET studies, a single oral dose of 60 mg was sufficient to achieve significant D3 receptor blockade, indicating favorable exposure. No detailed PK parameters (t1/2, Cmax) are provided.
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| Toxicity/Toxicokinetics |
In preclinical studies, GSK598809 demonstrated good safety properties at pharmacologically active doses. In human studies, it was well-tolerated, and no severe adverse events were reported in the PET imaging studies. Detailed toxicology data, such as a NOAEL, are not publicly available in this dataset.
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| References |
[1]. Dopamine D3 Receptor Antagonist (GSK598809) Potentiates the Hypertensive Effects of Cocaine in Conscious, Freely-Moving Dogs. J Pharmacol Exp Ther. 2015 Sep;354(3):484-92.
[2]. 1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: a new series of potent and selective dopamine D(3) receptor antagonists. J Med Chem. 2010 Jan 14;53(1):374-91 |
| Additional Infomation |
GSK598809 progressed to Phase I clinical trials as a potential treatment for substance use disorders by reducing drug craving. It has been used as a pharmacological tool to investigate the role of D3 receptors in reward processing, craving, and attentional bias, including studies on nicotine, alcohol, and food cue reactivity in human subjects.
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| Molecular Formula |
C22H23F4N5OS
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|---|---|
| Molecular Weight |
481.509536981583
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| Exact Mass |
481.155
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| CAS # |
863680-45-9
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| Related CAS # |
(-)-GSK598809 hydrochloride;863766-31-8; 863680-46-0; 863680-45-9; 1310803-30-5; 1008521-08-1 (tartrate); 1008521-09-2 (tartrate hydrate)
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| PubChem CID |
24743758
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
704
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(OC=N1)C2=NN=C(N2C)SCCCN3CC4CC4(C3)C5=C(C=C(C=C5)C(F)(F)F)F
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| InChi Key |
ZKRWPAYTJMRKLJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23F4N5OS/c1-13-18(32-12-27-13)19-28-29-20(30(19)2)33-7-3-6-31-10-15-9-21(15,11-31)16-5-4-14(8-17(16)23)22(24,25)26/h4-5,8,12,15H,3,6-7,9-11H2,1-2H3
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| Chemical Name |
5-[5-[3-[1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexan-3-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole
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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: 83.33 mg/mL (173.06 mM)
1M HCl: 28.57 mg/mL (59.33 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0768 mL | 10.3840 mL | 20.7680 mL | |
| 5 mM | 0.4154 mL | 2.0768 mL | 4.1536 mL | |
| 10 mM | 0.2077 mL | 1.0384 mL | 2.0768 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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