| 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 |
COR659 targets the GABAB receptor as a positive allosteric modulator and the cannabinoid CB1 receptor as an antagonist/inverse agonist. Its dual mechanism of action contributes to its behavioral effects. The compound is a 2-acylaminothiophene derivative.
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| ln Vitro |
It appears that COR659 works through a combination of mechanisms, including as activation at the cannabinoid CB1 receptor and positive allosteric regulation of the GABAB receptor[3].
In cell-free systems, COR659 acts as a positive allosteric modulator of the GABAB receptor. It enhances GABAB receptor signaling in the presence of GABA. The compound's activity at the CB1 receptor is characterized as antagonism or inverse agonism. In vitro metabolism studies have identified the methyl ester at C-3 of thiophene as a major site of metabolic liability. Cellular assays demonstrate that COR659 modulates GABAB receptor function through positive allosteric modulation. The compound enhances receptor signaling in cells expressing GABAB receptors. Its CB1 receptor antagonist/inverse agonist activity is confirmed in cells expressing CB1 receptors. These dual activities contribute to its unique pharmacological profile. |
| ln Vivo |
In food-deprived Wistar rats, the COR659 (0, 2.5, 5 and 10 mg/kg) therapy has no effect at all on lever-responding (FR10) for ordinary food pellets[1]. Lever-responding for a chocolate solution in Wistar rats and a sucrose solution in sP rats can be suppressed by COR659[2].
In vivo, COR659 suppresses alcohol and chocolate self-administration in rats. It also suppresses cue-induced reinstatement of chocolate seeking. The compound has an anorectic effect in rat models of overeating. Its behavioral effects are exerted via a composite mechanism involving GABAB PAM activity and CB1 antagonism/inverse agonism. |
| Enzyme Assay |
In vitro metabolism studies on COR659 are performed using liver microsomes or hepatocytes. The compound is incubated with metabolic enzymes, and metabolites are identified by LC-MS/MS. The methyl ester at C-3 of thiophene is identified as a major site of metabolic liability. GABAB receptor PAM activity is assessed using cell-based functional assays.
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| Cell Assay |
Cellular assays for COR659 are conducted using cells expressing GABAB receptors or CB1 receptors. GABAB PAM activity is assessed by measuring receptor signaling in the presence of GABA and varying concentrations of COR659. CB1 receptor activity is assessed by measuring inverse agonist or antagonist effects on constitutive or agonist-induced signaling.
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| Animal Protocol |
Animal/Disease Models: Male sP and Wistar rats[1].
Doses: 0, 2.5, 5 and 10 mg/kg. Route of Administration: intraperitoneally (ip) (administered 30 min before the start of the self-administration, reinstatement, and locomotor activity sessions.). Experimental Results: The magnitude of the reducing effect of the compound on number of lever-responses for alcohol averaged approximately 30, 55, and 70%, in comparison to the vehicle-treated rat group, in the rat groups treated with 2.5, 5, and 10 mg/kg COR659, respectively. The magnitude of the reducing effect of COR659 on number of lever-responses for alcohol averaged approximately 20, 40, and 80%, in comparison to the vehicle treated rat group, in the rat groups treated with 2.5, 5, and 10 mg/kg COR659, respectively. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies in rats have been performed on COR659. The compound's methyl ester at C-3 of thiophene is a major site of in vivo metabolic liability. Metabolically protected derivatives have been synthesized to improve PK properties. Detailed PK parameters including half-life and bioavailability have been characterized.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for COR659 are limited. In animal studies, the compound is administered at doses that suppress alcohol and chocolate self-administration without significant adverse effects. Comprehensive toxicological studies would be required for therapeutic development.
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| References |
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| Additional Infomation |
COR659 is a research compound with anti-addictive properties. It suppresses alcohol and chocolate self-administration in rats. Its dual mechanism of action at GABAB and CB1 receptors makes it a valuable tool for studying addiction and eating disorders. Metabolically protected derivatives have been developed to improve pharmacokinetic properties.
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| Molecular Formula |
C16H16CLNO3S
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|---|---|
| Molecular Weight |
337.821142196655
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| Exact Mass |
337.053
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| CAS # |
544450-68-2
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| PubChem CID |
897320
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
412
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)C(NC1=C(C(=O)OC)C(=C(C)S1)CC)=O
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| InChi Key |
AAFLALGGEYRGTR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H16ClNO3S/c1-4-12-9(2)22-15(13(12)16(20)21-3)18-14(19)10-5-7-11(17)8-6-10/h5-8H,4H2,1-3H3,(H,18,19)
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| Chemical Name |
methyl 2-[(4-chlorobenzoyl)amino]-4-ethyl-5-methylthiophene-3-carboxylate
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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: 25 mg/mL (74.00 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.40 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 25.0 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: 2.5 mg/mL (7.40 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (7.40 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 | 2.9602 mL | 14.8008 mL | 29.6016 mL | |
| 5 mM | 0.5920 mL | 2.9602 mL | 5.9203 mL | |
| 10 mM | 0.2960 mL | 1.4801 mL | 2.9602 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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