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| 5mg |
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Basimglurant (RG7090; RO491752) is a potent, selective and orally bioavailable mGlu5 negative allosteric modulator with a Kd of 1.1 nM. It is under Phase 2 clinical trial for treating MDD and Fragile X syndrome (FXS). Basimglurant is a promising novel medicine for psychiatric diseases. Basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features which suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy.
| Targets |
mGlu5 negative allosteric modulator (Ki = 1.2 nM for human mGlu5; IC₅₀ = 2.9 nM for inhibition of glutamate-induced Ca²⁺ mobilization in HEK293 cells); >1,000-fold selective over mGlu1–4,7–8 and unrelated targets (e.g., ion channels, transporters).[1]
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| ln Vitro |
In HEK293 cells expressing human mGlu5, basimglurant inhibited glutamate-induced Ca²⁺ mobilization with IC₅₀ = 2.9 nM. It also blocked DHPG-induced ERK1/2 phosphorylation (IC₅₀ = 7.3 nM) and internalization of mGlu5 receptors.[1]
In rat primary cortical neurons, basimglurant suppressed quisqualate-induced mGlu5-dependent cAMP accumulation (IC₅₀ = 8.2 nM) and reversed MPEP-induced increases in long-term potentiation (LTP).[1] Cell viability assays showed no cytotoxicity up to 10 μM in HEK293 and neuronal cells.[2] |
| ln Vivo |
In rat forced swim test (FST), oral basimglurant (0.3–3 mg/kg) reduced immobility time by 30–50% (p<0.01), comparable to imipramine. Effects were absent in mGlu5 knockout mice, confirming target specificity.[1]
In mouse tail suspension test (TST), basimglurant (1–10 mg/kg p.o.) decreased immobility by 40% (p<0.001). It also normalized stress-induced hyperthermia in mice at 3 mg/kg.[1] Chronic mild stress (CMS) model: 28-day treatment (1 mg/kg/day p.o.) reversed anhedonia in sucrose preference test (p<0.01) and reduced corticosterone levels.[1] |
| Enzyme Assay |
Radioligand binding assays used [³H]methoxyPEPy to measure affinity at human mGlu5 membranes. Basimglurant exhibited Ki = 1.2 nM with Hill slopes near unity, indicating absence of cooperativity.[1]
Functional antagonism was quantified via FLIPR Ca²⁺ flux assays in mGlu5-expressing HEK293 cells using glutamate EC₈₀ concentrations.[2] |
| Cell Assay |
Calcium mobilization: Cells loaded with Ca²⁺-sensitive dye were stimulated with glutamate, and fluorescence was measured. Basimglurant was pre-incubated 15 min before agonist addition.[1]
ERK phosphorylation: After DHPG stimulation, cells were lysed, and phospho-ERK levels were assessed via Western blot.[1] |
| Animal Protocol |
Acute models: Administered orally (0.3–10 mg/kg) as suspension in 0.5% methylcellulose 60 min pre-test in FST/TST.[1]
Chronic models: CMS rats received 1 mg/kg/day p.o. for 28 days; corticosterone measured via trunk blood collection.[1] Microdialysis: Subcutaneous (s.c.) administration (1–3 mg/kg) for monitoring prefrontal cortex glutamate release.[1] |
| ADME/Pharmacokinetics |
Oral bioavailability in rats: 69–78%. Plasma protein binding >99% across species.[1]
Half-life (t₁/₂): 2.1–3.0 h (rat), 4.5 h (dog). Brain-to-plasma ratio: 0.7 in rats after 3 mg/kg p.o.[1] Metabolized primarily by CYP3A4; major metabolites inactive.[2] |
| Toxicity/Toxicokinetics |
No significant hERG inhibition (IC₅₀ > 30 μM). LD₅₀ > 2,000 mg/kg p.o. in rats.[2]
28-day rat toxicity study: NOAEL = 30 mg/kg/day. No hepatotoxicity or histopathological changes observed.[1] |
| References |
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| Additional Infomation |
Acute models: Administered orally (0.3–10 mg/kg) as suspension in 0.5% methylcellulose 60 min pre-test in FST/TST.[1]
Chronic models: CMS rats received 1 mg/kg/day p.o. for 28 days; corticosterone measured via trunk blood collection.[1] Microdialysis: Subcutaneous (s.c.) administration (1–3 mg/kg) for monitoring prefrontal cortex glutamate release.[1] Basimglurant has been used in trials studying the diagnostic and treatment of Depression, Fragile X Syndrome, and Major Depressive Disorder. |
| Molecular Formula |
C18H13CLFN3
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|---|---|
| Molecular Weight |
325.767326116562
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| Exact Mass |
423.045
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| Elemental Analysis |
C, 66.36; H, 4.02; Cl, 10.88; F, 5.83; N, 12.90
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| CAS # |
1034442-21-1
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| Related CAS # |
802906-73-6 (Sulfate);1034442-21-1;
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| PubChem CID |
11438771
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.5
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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 |
23
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| Complexity |
465
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C=CN=1)C#CC1=C(C)N(C2C=CC(=CC=2)F)C(C)=N1
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| InChi Key |
UPZWINBEAHDTLA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H13ClFN3/c1-12-17(8-3-14-9-10-21-18(19)11-14)22-13(2)23(12)16-6-4-15(20)5-7-16/h4-7,9-11H,1-2H3
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| Chemical Name |
2-chloro-4-((1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-yl)ethynyl)pyridine
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| Synonyms |
RG-7090 RG 7090 RG7090 RO4917523 RO 4917523 RO-4917523 CTEP Derivative Basimglurant
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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 | 3.0697 mL | 15.3483 mL | 30.6965 mL | |
| 5 mM | 0.6139 mL | 3.0697 mL | 6.1393 mL | |
| 10 mM | 0.3070 mL | 1.5348 mL | 3.0697 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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