| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
The primary target of DS2 is the δ subunit-containing GABAA receptor, specifically the α4β3δ subtype. GABAA receptors are the major mediators of fast inhibitory synaptic transmission in the brain. Upon binding of the neurotransmitter GABA, the receptor undergoes a conformational change that opens its central pore, allowing chloride ions to flow into the neuron. This influx of negative charge hyperpolarizes the neuron, making it less likely to fire. The δ subunit is primarily found in extrasynaptic locations, where it mediates "tonic" inhibition—a sustained, low-level inhibition that is crucial for controlling neuronal excitability. By positively modulating these δ-containing receptors, DS2 enhances the effect of GABA, increasing the magnitude of tonic inhibition. This selective modulation is a key feature that distinguishes it from non-selective GABAA modulators like benzodiazepines or barbiturates.
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| ln Vitro |
DS2 is a potent and selective positive allosteric modulator of δ-GABAA receptors. It selectively potentiates GABA responses mediated by α4β3δ receptors. This selectivity is crucial for its utility as a research tool, as it allows for the dissection of the specific roles of δ-GABAA receptors without the confounding effects of modulating other GABAA receptor subtypes. It does not enhance the activity of α4β3γ2 or α1β3γ2 receptors, which are the primary targets of benzodiazepines. In vitro, DS2's activity is typically characterized using electrophysiological techniques, such as patch-clamp recording, on cells expressing recombinant GABAA receptors. In these assays, DS2 is co-applied with GABA, and its ability to potentiate the GABA-induced current is measured.
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| ln Vivo |
DS2 has been studied in vivo for its potential therapeutic effects. Its selective modulation of δ-GABAA receptors has shown promise in the context of pain and sleep disorders. By enhancing tonic inhibition, DS2 can reduce neuronal hyperexcitability, which is a key feature in chronic pain conditions. It has also been suggested that δ-GABAA receptors play a role in sleep regulation, and DS2 could be a useful tool for studying this. Specific in vivo studies have shown that DS2 can relieve pain, supporting its potential as an analgesic. These findings highlight the importance of δ-GABAA receptors as a target for therapeutic intervention.
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| Enzyme Assay |
The in vitro receptor binding/electrophysiology assay for DS2 typically involves the use of patch-clamp electrophysiology on cells expressing recombinant δ-GABAA receptors. Human embryonic kidney (HEK) cells are transfected with cDNAs encoding the α4, β3, and δ subunits to form the α4β3δ receptor. In the whole-cell patch-clamp configuration, the cell is held at a negative membrane potential (e.g., -70 mV). GABA is applied to the cell to evoke a chloride current. DS2 is then co-applied with GABA, and the increase in the current amplitude is measured. The percent potentiation is calculated and plotted against the compound concentration to determine its potency. This is a highly sensitive and direct method for assessing the activity of modulators at ligand-gated ion channels.
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| Cell Assay |
In vitro cell-based assays for DS2 are typically the same as the receptor assays described above, as the functional readout is the potentiation of the GABA-induced current. There are no standard cell viability or signaling assays for this type of modulator, as its activity is defined by its effect on ion channel function. Therefore, the primary cell-based assay for DS2 is electrophysiological recording from cells expressing the target receptor.
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| Animal Protocol |
In vivo animal studies for DS2 are conducted to evaluate its potential therapeutic effects. For pain research, rodent models of pain, such as the formalin test, the hot plate test, or models of neuropathic pain (e.g., chronic constriction injury, CCI), are used. DS2 is administered (likely via intraperitoneal or oral route), and its effect on pain-related behaviors is assessed. For sleep studies, electroencephalography (EEG) and electromyography (EMG) recordings are performed in rodents to analyze sleep-wake cycles. These studies are crucial for translating the in vitro findings into a meaningful in vivo context.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for DS2 is not extensively reported in the provided search results. Its molecular weight is 353.83, which is within the range for good oral bioavailability. As a research compound, its ADME properties would be determined in preclinical studies.
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| Toxicity/Toxicokinetics |
Specific toxicity data for DS2 is not publicly available. As a positive allosteric modulator of GABAA receptors, there is a potential for on-target side effects, such as sedation or ataxia, especially at high doses. Its selectivity for the δ subunit may confer a more favorable side effect profile compared to non-selective modulators. It is classified as a research tool and is not intended for human use.
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| References | |
| Additional Infomation |
DS2 is a valuable research tool for studying the role of δ-GABAA receptors in the central nervous system. Its high selectivity for δ-containing receptors makes it the compound of choice for probing the function of these receptors in various physiological and pathological processes, including pain, anxiety, sleep, and epilepsy. The compound has not advanced to clinical trials and does not have FDA approval for any indication.
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| Molecular Formula |
C18H12CLN3OS
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| Molecular Weight |
353.82
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| Exact Mass |
353.039
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| CAS # |
374084-31-8
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| PubChem CID |
979718
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| Appearance |
Off-white to light brown solid powder
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| LogP |
5.352
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
458
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AZKMWHRDICVYEI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H12ClN3OS/c19-13-8-6-12(7-9-13)18(23)21-17-16(14-4-3-11-24-14)20-15-5-1-2-10-22(15)17/h1-11H,(H,21,23)
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| Chemical Name |
4-chloro-N-(2-thiophen-2-ylimidazo[1,2-a]pyridin-3-yl)benzamide
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| Synonyms |
DS 2; DS-2; DS2
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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 | 2.8263 mL | 14.1315 mL | 28.2630 mL | |
| 5 mM | 0.5653 mL | 2.8263 mL | 5.6526 mL | |
| 10 mM | 0.2826 mL | 1.4131 mL | 2.8263 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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