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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.
Physicochemical Properties
| 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) |
Biological Activity
| 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 |
[1]. Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. J Pharmacol Exp Ther. 2015 Apr;353(1):213-33. [2]. Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases. J Med Chem. 2015 Feb 12;58(3):1358-71. |
| 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. |
Solubility Data
| 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. 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. 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 corn oil and mix evenly. (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 |