| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
GSK598809 targets the dopamine D3 receptor (DRD3), which is highly expressed in limbic regions and mediates reward and motivation. By antagonising D3, it reduces the incentive salience of drug‑paired cues, potentially preventing relapse.
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| ln Vitro |
In vitro, GSK598809 shows high affinity for D3 receptor with pKi 8.9, and selectivity over D2 and other dopamine receptors. It blocks dopamine‑induced signalling in D3‑expressing cell lines, confirming its antagonistic properties.
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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, preclinical studies demonstrate that GSK598809 decreases cue‑induced reinstatement of drug‑seeking behaviour in animal models. It has progressed to Phase I clinical trials, indicating favourable PK and safety in humans for further evaluation. |
| Enzyme Assay |
D3 receptor binding affinity is determined by radioligand displacement using [³H]spiperone and membrane preparations from D3‑expressing cells; non‑specific binding is defined with excess competitor, and Ki is calculated. Selectivity is assessed against D2 and other receptors.
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| Cell Assay |
Cell‑based assays use CHO cells expressing human D3 receptor; dopamine‑induced calcium flux or cAMP modulation is measured in the presence of GSK598809 to quantify antagonism.
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| Animal Protocol |
In vivo preclinical models of cocaine addiction involve administering GSK598809 and measuring drug‑seeking behaviour (e.g., lever pressing) under cue‑induced reinstatement paradigms. Dosing routes (oral or i.p.) and timing are evaluated.
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| ADME/Pharmacokinetics |
GSK598809 has been evaluated in Phase I trials; oral bioavailability and half‑life are suitable for once‑daily dosing. Detailed PK data are proprietary, but its progression to clinical trials indicates adequate exposure and tolerability.
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| Toxicity/Toxicokinetics |
Phase I data suggest acceptable safety; common side effects may include neurological effects due to D3 antagonism, but selectivity minimises extrapyramidal symptoms. Long‑term safety for addiction treatment would require further trials.
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| References | |
| Additional Infomation |
Dopamine D3 receptor antagonists
GSK598809 is an investigational compound that has reached Phase I for cocaine dependence. It represents a novel approach to treating substance use disorders by targeting cue‑induced craving. Further clinical development is needed to establish efficacy. |
| Molecular Formula |
C22H23F4N5OS
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|---|---|
| Molecular Weight |
481.51
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| CAS # |
1310803-30-5
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| Related CAS # |
(-)-GSK598809 hydrochloride;863766-31-8;(-)-GSK598809;863680-46-0; 863680-45-9; 1310803-30-5; 1008521-08-1 (tartrate); 1008521-09-2 (tartrate hydrate)
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| PubChem CID |
71587973
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5.02
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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 |
34
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| Complexity |
749
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=C(OC=N1)C2=NN=C(N2C)SCCCN3C[C@@]4(C[C@@]4(C3)C5=C(C=C(C=C5)C(F)(F)F)F)C
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| InChi Key |
BAFWBNHYBAXTSE-FCHUYYIVSA-N
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| InChi Code |
InChI=1S/C23H25F4N5OS/c1-14-18(33-13-28-14)19-29-30-20(31(19)3)34-8-4-7-32-11-21(2)10-22(21,12-32)16-6-5-15(9-17(16)24)23(25,26)27/h5-6,9,13H,4,7-8,10-12H2,1-3H3/t21-,22+/m0/s1
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| Chemical Name |
5-(5-((3-((1S,5R)-1-(2-Fluoro-4-(trifluoromethyl)phenyl)-5-methyl-3-azabicyclo(3.1.0)hexan-3-yl)propyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)-4-methyloxazole
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| Synonyms |
GSK-598809; GSK598809; 1310803-30-5; 5-[5-[3-[(1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-methyl-3-azabicyclo[3.1.0]hexan-3-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole; BAFWBNHYBAXTSE-FCHUYYIVSA-N; SCHEMBL29462341; DTXSID40156878; GSK 598809;
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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) |
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
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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 | 2.0768 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.
Link: https://clinicaltrials.gov/ct2/show/NCT00437840
Conditions:Substance DependenceLink: https://clinicaltrials.gov/ct2/show/NCT00728897
Conditions:Substance DependenceLink: https://clinicaltrials.gov/ct2/show/NCT00728052
Conditions:Substance Dependence
Title:Study To Investigate If Repeat Doses Of GSK598809 Are Safe And Well Tolerated And To Evaluate Blood Levels Of GSK598809
Status:Completed
updateDate:2017-07-31
Ctid:NCT00437632
Link: https://clinicaltrials.gov/ct2/show/NCT00437632
Conditions:Substance DependenceLink: https://clinicaltrials.gov/ct2/show/NCT00605241
Conditions:Substance DependenceLink: https://clinicaltrials.gov/ct2/show/NCT00887367
Conditions:Substance DependenceLink: https://clinicaltrials.gov/ct2/show/NCT01039454
Conditions:Substance DependenceLink: https://clinicaltrials.gov/ct2/show/NCT01188967
Conditions:Nicotine DependenceLink: https://clinicaltrials.gov/ct2/show/NCT00793468
Conditions:Substance DependenceLink: https://clinicaltrials.gov/ct2/show/NCT00908206
Conditions:Substance Dependence|Alcohol DependenceLink: https://clinicaltrials.gov/ct2/show/NCT00468806
Conditions:Healthy Subjects Effects of oral GSK598809 and intravenous cocaine on peak mean arterial blood pressure in dogs.J Pharmacol Exp Ther.2015 Sep;354(3):484-92. |
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 Time courses of heart rate in unrestrained dogs treated with combinations of oral GSK598809 and intravenous cocaine.J Pharmacol Exp Ther.2015 Sep;354(3):484-92. |
 Time courses of mean arterial blood pressure in unrestrained dogs treated with combinations of oral GSK598809 and intravenous cocaine.J Pharmacol Exp Ther.2015 Sep;354(3):484-92. |
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