| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Basimglurant sulfate (RG7090; RO491752) is a potent, selective and orally bioavailable mGlu5 negative allosteric modulator with a Kd of 1.1 nM. It is being studied in a Phase 2 clinical trial to treat FXS and MDD. A promising new treatment for psychiatric conditions is basimglurant. Due to its advantageous drug-like characteristics, distinct molecular mechanism of action, and antidepressant-like qualities, basimglurant may also be able to treat significant MDD comorbidities like pain and anxiety, as well as daytime sleepiness, apathy, and lethargy.
| Targets |
mGlu5 Receptor ( Kd = 1.1 nM );
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]
|
|---|---|
| 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] [3H]-basimglurant saturation analysis of recombinant human mGlu5 shows a single-phase saturation isotherm with a Kd of 1.1 nM. In competition binding experiments with human recombinant mGlu5, Basimglurant (RG7090) completely replaced [3H]-MPEP with a Ki of 35.6 nM and [3H]-ABP688 with a Ki of 1.4 nM. In HEK293 cells stably expressing human mGlu5, Basimglurant (RG7090) inhibits quiescentine-induced Ca2+ mobilization with an IC50 of 7.0 nM and inhibits [3H]-inositol phosphate accumulation with an IC50 of 5.9 nM. Basimglurant (RG7090) shows similar potency in radioligand binding and functional assays of human and rodent mGlu5 receptor orthologues [1]. |
| 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] Basimglurant (RG7090) is a potent, selective and safe mGlu5 inhibitor with good oral bioavailability and long half-life supporting once-daily dosing, good brain penetration and high in vivo potency. It has antidepressant properties, confirmed by its functional magnetic imaging (fMRI) profile, as well as anxiolytic and antinociceptive properties [1]. It is currently in Phase II clinical studies for the treatment of depression and fragile X syndrome. Basimglurant dose-dependently increased drinking duration in the Vogel conflict drinking test. Total plasma exposure at effective doses of Basimglurant (RG7090) ranges from 5 ng/mL (0.03 mg/kg) to 37 ng/mL (0.3 mg/kg) [2]. |
| 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 |
|
| Additional Infomation |
Basimglurant is the first mGlu5 NAM advanced to Phase II clinical trials for major depressive disorder (MDD) and treatment-resistant depression (TRD).[1]
Mechanism: Modulates glutamatergic neurotransmission without blocking ionotropic receptors, reducing side-effect risks vs. ketamine.[2] Clinical efficacy: Demonstrated significant improvement in MADRS scores vs. placebo in a Phase II study (NCT01437657).[1] Basimglurant has been used in trials studying the diagnostic and treatment of Depression, Fragile X Syndrome, and Major Depressive Disorder. |
| Molecular Formula |
C18H13CLFN3
|
|---|---|
| Molecular Weight |
325.76700
|
| Exact Mass |
325.078
|
| Elemental Analysis |
C, 66.36; H, 4.02; Cl, 10.88; F, 5.83; N, 12.90
|
| CAS # |
802906-73-6
|
| Related CAS # |
802906-73-6 (Sulfate); 1034442-21-1
|
| PubChem CID |
11438771
|
| Appearance |
Off-white to yellow solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
526.6±60.0 °C at 760 mmHg
|
| Flash Point |
272.3±32.9 °C
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
| Index of Refraction |
1.604
|
| LogP |
4.49
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
23
|
| Complexity |
465
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C=CC(N2C(C)=C(C#CC3C=C(Cl)N=CC=3)N=C2C)=CC=1
|
| InChi Key |
RPRPXJNEEIIWAL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H13ClFN3.H2O4S/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;1-5(2,3)4/h4-7,9-11H,1-2H3;(H2,1,2,3,4)
|
| Chemical Name |
2-chloro-4-((1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-yl)ethynyl)pyridine sulfate
|
| Synonyms |
RO4917523 sulfate;RG-7090 sulfate; RG 7090 sulfate; Basimglurant; 802906-73-6; CTEP Derivative; 2-Chloro-4-((1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-yl)ethynyl)pyridine; Ro4917,523; RO-4917523; RO 4917523 sulfate; RG7090 sulfate; RO-4917523; Basimglurant sulfate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ≥ 33.33 mg/mL (~102.3 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.67 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 (7.67 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 heating and sonication. 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 (7.67 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 | 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
