| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
mGlu5 18.2 nM (Ki)
ML353 selectively targets the metabotropic glutamate receptor 5 (mGlu5) with sub-100 nM affinity, displaying >200-fold selectivity over other mGlu receptor subtypes (mGlu1, 2-4, 6-8). It is an MPEP-site silent allosteric modulator (SAM) that binds to the same allosteric site as MPEP but behaves as a neutral antagonist rather than an inverse agonist. |
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| ln Vitro |
In PBS (PH=7.4), ML353 is a completely soluble molecule that dissolves at 16.9 µM or 6.0 µg/mL [1]. Good stability is exhibited by ML353 in PBS buffer [1].
ML353 is a fully soluble molecule with high affinity for mGlu5, exhibiting a Ki value of 18.2 nM. It improves the affinity of common allosteric sites by 20-fold over the previous mGlu5 SAM tool compound, 5mpep. In PBS (pH=7.4), it dissolves at 16.9 uM (6.0 ug/mL) and demonstrates excellent stability. It has a solubility of 16.9 uM or 6.0 ug/mL in PBS. |
| ln Vivo |
Not available. The compound's mechanism of action as a SAM makes it a powerful tool for studying the nuanced pharmacology of mGlu5, such as its basal activity and how it modulates the effects of orthosteric glutamate, but no quantitative in vivo data for ML353 itself is presented.
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| Enzyme Assay |
Standard binding assays to assess ML353's affinity for mGlu5 involve using membranes prepared from cells expressing human mGlu5. The assay uses a radioligand such as [3H]MPEP or another high-affinity mGlu5 allosteric ligand. The membrane preparation is incubated with a fixed concentration of the radioligand and increasing concentrations of ML353. Non-specific binding is determined in the presence of a high concentration of a competitor. After incubation, bound ligand is separated by rapid filtration through glass fiber filters, and the radioactivity retained on the filters is measured to calculate specific binding and Ki values.
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| Cell Assay |
Standard cellular protocols for assessing mGlu5 antagonist activity involve using cell lines (e.g., HEK293 or CHO cells) stably expressing the human mGlu5 receptor and a calcium-sensitive dye (like Fluo-4). Cells are loaded with the dye, and then pre-incubated with varying concentrations of ML353. Subsequently, an agonist such as glutamate or DHPG is added to activate the receptor, and the resulting increase in intracellular calcium is measured using a fluorescence plate reader. A decrease in the calcium signal indicates antagonist activity.
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| Animal Protocol |
Not available. As a research compound, its in vivo behavior is not well-documented. A typical in vivo protocol for mGlu5 modulators would involve dosing mice (e.g., via intraperitoneal injection) in models of anxiety, pain, or addiction, followed by behavioral testing and subsequent tissue collection for ex vivo receptor occupancy studies or biomarker analysis.
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| ADME/Pharmacokinetics |
ML353 is a fully soluble molecule with high affinity for mGlu5. It has a solubility of 16.9 uM or 6.0 ug/mL in PBS. For in vivo studies, it can be formulated in various vehicles, such as 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline, which is typical for many CNS-penetrant compounds.
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| Toxicity/Toxicokinetics |
As a highly selective mGlu5 probe, ML353's toxicity is expected to be low at pharmacologically relevant doses. No specific toxicological data is provided, but off-target effects are minimized due to its >200-fold selectivity over other mGlu receptors. Studies with other mGlu5 antagonists suggest they are generally well-tolerated in rodents at doses sufficient to engage the target.
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| References | |
| Additional Infomation |
ML353 is a high-quality chemical probe from the NIH Molecular Libraries Program. Its purpose is to solve the intrinsic activity of silent allosteric modulators in vivo, essentially serving as a "drug blocker" to isolate the specific role of mGlu5 in CNS disorders. It is strictly for laboratory research and is not a clinical candidate, nor is it part of any approved therapy.
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| Molecular Formula |
C19H15FN2O
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|---|---|
| Molecular Weight |
306.33
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| CAS # |
2990506-75-5
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| Appearance |
White to off-white solid powder
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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 | 3.2645 mL | 16.3223 mL | 32.6445 mL | |
| 5 mM | 0.6529 mL | 3.2645 mL | 6.5289 mL | |
| 10 mM | 0.3264 mL | 1.6322 mL | 3.2645 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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