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Purity: ≥98%
CFMTI is a novel, potent and selective allosteric antagonist of metabotropic glutamate receptor (mGluR) 1 with IC50 of 2.6 nM. In vitro and in vivo, oral administration of CFMTI exhibited strong and specific antagonistic activity on mGluR1. Through IC(50) values of 2.6 and 2.3 nM, respectively, CFMTI inhibited the intracellular Ca(2+) mobilization induced by L-glutamate in Chinese hamster ovary cells that expressed rat and human mGluR1a. CFMTI demonstrated no agonistic or antagonistic actions toward other mGluR subtypes or other receptors at 10 microM, and its selectivity to mGluR1 over mGluR5 was >2000-fold. In mice given (S)-3,5-dihidroxyphenylglycine, it inhibited face-washing behavior at doses ranging from 3 to 30 mg/kg, with 73 to 94% receptor occupancy. At therapeutic doses, CFMTI did not result in hypolocomotion or motor incoordination, in contrast to clozapine. CFMTI and clozapine increased the number of fos-positive neurons in the medial prefrontal cortex and nucleus accumbens but not in the dorsolateral striatum in c-fos expression studies. These findings imply that rather than being more like typical antipsychotics, mGluR1 antagonists' antipsychotic activities are more like those of atypical antipsychotics.
| Targets |
Human mGluR1a ( IC50 = 2.6 nM ); Rat mGluR1a ( IC50 = 2.3 nM )
Metabotropic glutamate receptor 1 (mGluR1) (human mGluR1a: IC50=2.6 nM; rat mGluR1a: IC50=2.3 nM); Selectivity over mGluR5 is >2000-fold[1] |
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| ln Vitro |
1. CFMTI inhibited L-glutamate-induced intracellular Ca²⁺ mobilization in Chinese hamster ovary (CHO) cells expressing human mGluR1a with an IC50 value of 2.6 nM [1]
2. CFMTI inhibited L-glutamate-induced intracellular Ca²⁺ mobilization in CHO cells expressing rat mGluR1a with an IC50 value of 2.3 nM [1] |
| ln Vivo |
of 3 to 30 mg/kg, with a receptor occupancy of 73 to 94% [1]
2. Orally administered CFMTI reduced methamphetamine-induced hyperlocomotion and disruption of prepulse inhibition (PPI) at the dose range of 3 to 30 mg/kg, which was the same as the dose range required to antagonize the face-washing behavior, similar to haloperidol and clozapine [1] 3. CFMTI and clozapine improved ketamine-induced hyperlocomotion, PPI disruption and MK-801-induced social withdrawal without any cataleptogenic activities, while haloperidol only improved ketamine-induced hyperlocomotion [1] 4. Unlike clozapine, CFMTI caused neither hypolocomotion nor motor incoordination at therapeutic doses [1] 5. CFMTI increased the number of fos-positive neurons in the nucleus accumbens and medial prefrontal cortex but not in the dorsolateral striatum in c-fos expression studies, consistent with clozapine [1] |
| Enzyme Assay |
1. To determine the antagonistic activity of CFMTI on mGluR1, CHO cells expressing human or rat mGluR1a were exposed to L-glutamate to induce intracellular Ca²⁺ mobilization, and different concentrations of CFMTI were added to the cell culture system. The changes in intracellular Ca²⁺ levels were detected to calculate the IC50 value of CFMTI for inhibiting Ca²⁺ mobilization [1]
2. To evaluate the receptor selectivity of CFMTI, the compound was applied to cells expressing mGluR5 and other mGluR subtypes at a concentration of 10 μM, and the agonistic or antagonistic activities of CFMTI on these receptors were detected by measuring the corresponding cellular responses [1] |
| Cell Assay |
1. CHO cells stably expressing human mGluR1a or rat mGluR1a were cultured in an appropriate medium. The cells were stimulated with L-glutamate to trigger intracellular Ca²⁺ mobilization, and then CFMTI at various concentrations was added to the cell culture. The intracellular Ca²⁺ concentration was measured using relevant detection methods to assess the inhibitory effect of CFMTI and calculate the IC50 values [1]
2. CHO cells expressing other mGluR subtypes (including mGluR5) were prepared, and CFMTI was added to the cell culture at a concentration of 10 μM. The cellular responses related to receptor activation or inhibition were detected to determine whether CFMTI had agonistic or antagonistic effects on these receptors [1] |
| Animal Protocol |
1. Face-washing behavior assay: Mice were treated with (S)-3,5-dihydroxyphenylglycine to induce face-washing behavior, and then CFMTI was orally administered to the mice at doses of 3, 10, and 30 mg/kg. The face-washing behavior of the mice was observed and recorded, and the receptor occupancy of CFMTI on mGluR1 was determined [1]
2. Methamphetamine-induced hyperlocomotion and PPI disruption assay: Mice were given methamphetamine to induce hyperlocomotion and PPI disruption, followed by oral administration of CFMTI at the dose range of 3 to 30 mg/kg. The locomotor activity of the mice was measured using an automated activity monitoring system, and the PPI was evaluated by a prepulse inhibition test system. The effects of CFMTI were compared with those of haloperidol and clozapine [1] 3. Ketamine/MK-801-induced behavioral abnormality assay: Mice were treated with ketamine to induce hyperlocomotion and PPI disruption, or with MK-801 to induce social withdrawal. CFMTI was orally administered at the dose range of 3 to 30 mg/kg, and the locomotor activity, PPI, and social interaction behavior of the mice were assessed. The cataleptogenic activity of CFMTI was also evaluated by observing the catalepsy symptoms of the mice [1] 4. c-fos expression assay: Mice were orally administered with CFMTI, and after a certain period, the mice were sacrificed and brain tissues (nucleus accumbens, medial prefrontal cortex, dorsolateral striatum) were collected. The brain sections were prepared, and the number of fos-positive neurons was detected by immunohistochemical staining [1] |
| Toxicity/Toxicokinetics |
1. Unlike the typical antipsychotic drug haloperidol, CFMTI has not shown rigidity in animal studies [1]
2. Unlike clozapine, CFMTI does not cause hypokinesis or ataxia at therapeutic doses (3-30 mg/kg) [1] |
| References | |
| Additional Infomation |
1. CFMTI is a newly discovered selective metabolite glutamate receptor 1 allosteric antagonist[1]
2. The antipsychotic activity of CFMTI (mGluR1 antagonist) is more similar to that of atypical antipsychotics (such as clozapine) than that of atypical antipsychotics (such as haloperidol)[1] |
| Molecular Formula |
C19H16FN5O
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| Molecular Weight |
349.37
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| Exact Mass |
349.133
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| Elemental Analysis |
C, 65.32; H, 4.62; F, 5.44; N, 20.05; O, 4.58
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| CAS # |
864864-17-5
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| Related CAS # |
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| PubChem CID |
11175501
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
612.7±65.0 °C at 760 mmHg
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| Flash Point |
324.4±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.760
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| LogP |
0.97
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
558
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N(C2CC2)CC2C1=CC=C(C1=C(C)N(C3C(F)=NC=CC=3)N=N1)C=2
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| InChi Key |
XZBFQWRAIYRPPZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H16FN5O/c1-11-17(22-23-25(11)16-3-2-8-21-18(16)20)12-4-7-15-13(9-12)10-24(19(15)26)14-5-6-14/h2-4,7-9,14H,5-6,10H2,1H3
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| Chemical Name |
2-cyclopropyl-5-[1-(2-fluoropyridin-3-yl)-5-methyltriazol-4-yl]-3H-isoindol-1-one
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| Synonyms |
CFMTI
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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 |
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| 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) |
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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 | 2.8623 mL | 14.3115 mL | 28.6229 mL | |
| 5 mM | 0.5725 mL | 2.8623 mL | 5.7246 mL | |
| 10 mM | 0.2862 mL | 1.4311 mL | 2.8623 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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