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| 5mg |
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| 10mg |
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| 100mg |
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| Targets |
Dipraglurant targets the mGlu5 receptor as a negative allosteric modulator. By attenuating mGlu5 activity, it reduces excessive glutamate signaling implicated in movement disorders, neurodegeneration, and psychiatric conditions. It regulates excitatory glutamatergic neurotransmission in the central nervous system.
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| ln Vitro |
Quinpirole, a D2R agonist, and caged dopamine (NPEC-Dopamine) both cause aberrant membrane responses and calcium elevations that are counteracted by dipragrant (1–10 μM; 15 minutes) [3].
In vitro, dipraglurant (1-10 µM; 15 min) counteracts the abnormal membrane responses and calcium rise induced either by the D2R agonist quinpirole or by caged dopamine. It is a negative allosteric modulator of mGluR5 with high potency. |
| ln Vivo |
Dipraglurant (3–30 mg/kg; single oral dose) decreases chorea and dystonia brought on by levodopa and does not affect how well levodopa works to treat Parkinson's disease in handicapped macaques [1]. Following oral treatment (3, 10, 30 mg/kg), dipraglutan showed Cmax (1.040, 1.380, 5.310 ng/mL), Tmax (1.0, 0.5, 1.0 h), and AUCinf (2.230, 2.860, 15.700) in macaques [1].
In vivo, dipraglurant (3–30 mg/kg; single oral dose) decreases chorea and dystonia brought on by levodopa. It inhibits dyskinesia in the LID macaque model. It reduces levodopa-induced dyskinesia and muscle tone disturbances without interfering with the efficacy of levodopa treatment. |
| Enzyme Assay |
In vitro receptor binding assays for dipraglurant typically use membrane preparations from cells expressing mGluR5. Radiolabeled mGluR5 ligands are displaced by increasing concentrations of the compound to determine binding affinity. Functional assays measure the compound's ability to modulate mGluR5-mediated signaling. The compound's selectivity for mGluR5 over other mGlu receptors is assessed.
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| Cell Assay |
Cell-based functional assays for dipraglurant involve measuring its ability to inhibit mGluR5-mediated calcium mobilization or other signaling pathways in cells expressing the receptor. Cells are treated with the compound and stimulated with an mGluR5 agonist. Inhibition of signaling is quantified. The compound's effects on glutamate-induced calcium responses are measured.
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| Animal Protocol |
In vivo animal studies for dipraglurant typically involve oral administration to animal models of Parkinson's disease or levodopa-induced dyskinesia. Motor function is assessed using behavioral tests. The compound's ability to reduce dyskinesia without affecting the therapeutic effect of levodopa is evaluated. The MPTP macaque model is used for LID studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of dipraglurant are characteristic of orally active, brain-penetrant small molecules. The compound is absorbed following oral administration and crosses the blood-brain barrier. It has a half-life suitable for therapeutic applications. It is a metabolite glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM).
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| Toxicity/Toxicokinetics |
The toxicological profile of dipraglurant has been evaluated in preclinical and clinical studies. The compound is generally well-tolerated, with a favorable safety profile. Common side effects are mild and transient. Phase IIa trial data supports further clinical study.
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| References |
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| Additional Infomation |
Dipraglurant has been used in trials for the treatment of Parkinson's disease. It is a metabolite glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM).
Dipraglurant has been investigated clinically for levodopa-induced dyskinesia in Parkinson's disease. It has been used in trials for the treatment of Parkinson's disease. As of 2014, it was in phase II clinical trials. An extended-release formulation is being investigated for non-parkinsonian dystonia. |
| Molecular Formula |
C16H12FN3
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|---|---|
| Molecular Weight |
265.2914
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| Exact Mass |
265.102
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| CAS # |
872363-17-2
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| PubChem CID |
44557636
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| Appearance |
White to off-white solid powder
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| LogP |
2.852
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
386
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LZXMUJCJAWVHPZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H12FN3/c17-13-8-9-16-19-15(12-20(16)11-13)7-2-1-5-14-6-3-4-10-18-14/h3-4,6,8-12H,2,7H2
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| Chemical Name |
6-fluoro-2-(4-pyridin-2-ylbut-3-ynyl)imidazo[1,2-a]pyridine
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| Synonyms |
ADX 48621; ADX48621; ADX-48621
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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 : ≥ 40 mg/mL (~150.78 mM)
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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 | 3.7695 mL | 18.8473 mL | 37.6946 mL | |
| 5 mM | 0.7539 mL | 3.7695 mL | 7.5389 mL | |
| 10 mM | 0.3769 mL | 1.8847 mL | 3.7695 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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