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Purity: ≥98%
| Targets |
DFMTI targets the metabotropic glutamate receptor 1 (mGlu1), a G protein-coupled receptor that is activated by glutamate, the primary excitatory neurotransmitter in the central nervous system. mGlu1 is predominantly expressed in the brain, particularly in regions involved in motor coordination, learning, and memory. DFMTI is a negative allosteric modulator (NAM) of mGlu1, meaning it binds to an allosteric site on the receptor and reduces its response to glutamate without competing with the endogenous ligand. The compound can completely block the rmGlu1 L757V glutamate response. DFMTI exhibits a moderate decrease in human potency of approximately 3-fold when compared to rat.
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| ln Vitro |
DFMTI demonstrates potent in vitro activity as an mGlu1 negative allosteric modulator. The compound exhibits an IC50 of 4.3 ± 1.3 nM against mGluR1 receptors. In a head-to-head study, DFMTI showed an IC50 of 8 nM at rat mGluR1 and 31 nM at human mGluR1, representing only a 3.9-fold loss in potency. This relatively modest species difference contrasts favorably with other mGlu1 NAMs that show much larger potency shifts between rat and human. DFMTI can completely block the rmGlu1 L757V glutamate response. The compound's potent and selective mGlu1 antagonism makes it a valuable tool for studying the role of mGlu1 in neurological and psychiatric disorders.
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| ln Vivo |
DFMTI is efficacious in disrupting prepulse inhibition when dosed orally in rats. Prepulse inhibition is a measure of sensorimotor gating that is disrupted in various psychiatric disorders, including schizophrenia. The compound's ability to disrupt prepulse inhibition in rats suggests that mGlu1 modulation may be involved in sensorimotor gating processes. DFMTI exhibits a moderate decrease in human potency of approximately 3-fold when compared to rat. The compound's oral activity supports its utility for in vivo studies. Detailed in vivo efficacy data, including specific dosing regimens and effects on prepulse inhibition, are available in the primary literature.
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| Enzyme Assay |
The in vitro receptor binding and functional assay for DFMTI measures the compound's negative allosteric modulator activity at the mGlu1 receptor. Radioligand binding assays are performed using membrane preparations from cells expressing rat or human mGlu1 receptors. Varying concentrations of DFMTI are incubated with the membrane preparation and a radiolabeled mGlu1 ligand. For functional assays, cells expressing mGlu1 are loaded with a fluorescent calcium indicator and treated with varying concentrations of DFMTI prior to stimulation with glutamate. The inhibition of glutamate-induced calcium responses by DFMTI is measured, and IC50 values are determined (8 nM for rat mGluR1, 31 nM for human mGluR1). The compound is dissolved in DMSO and diluted in assay buffer. Appropriate positive controls and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for DFMTI is performed using cells expressing mGlu1 receptors, such as HEK293 cells stably transfected with rat or human mGlu1. Cells are cultured in appropriate medium and loaded with a fluorescent calcium indicator. Cells are treated with varying concentrations of DFMTI or vehicle control (DMSO) prior to stimulation with glutamate. Intracellular calcium levels are measured using a fluorescence plate reader. The inhibition of glutamate-induced calcium responses by DFMTI is quantified, and IC50 values are determined by fitting dose-response curves (8 nM for rat mGluR1, 31 nM for human mGluR1). The compound's effects on downstream signaling pathways can also be assessed. The compound's ability to block the rmGlu1 L757V glutamate response can be evaluated using mutant receptor-expressing cells.
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| Animal Protocol |
In vivo animal experiments with DFMTI are conducted using rodent models to assess the compound's effects on sensorimotor gating and other behavioral endpoints. DFMTI is administered orally due to its oral activity. Prepulse inhibition (PPI) of the acoustic startle response is measured to assess sensorimotor gating. The compound's ability to disrupt PPI is evaluated by comparing PPI levels in treated versus vehicle-treated animals. The compound's effects on other behavioral parameters can also be assessed. Body weight and general health status are monitored throughout the study. Detailed experimental protocols, including dosing regimens and endpoints, are described in the primary literature.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for DFMTI are not extensively documented in publicly available sources. The compound is described as orally active, indicating that it has adequate oral absorption for in vivo studies. DFMTI has a molecular weight of 368.38 and a chemical formula of C20H18F2N4O. The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, DFMTI is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for DFMTI are not extensively documented in publicly available sources. As a research-grade compound, DFMTI is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References | |
| Additional Infomation |
Structure in the first source
DFMTI is a research compound developed for studying the role of mGlu1 receptors in neurological and psychiatric disorders. The compound is a potent negative allosteric modulator of mGlu1 with IC50 values of 8 nM for rat mGluR1 and 31 nM for human mGluR1. DFMTI can completely block the rmGlu1 L757V glutamate response. The compound is efficacious in disrupting prepulse inhibition when dosed orally in rats, suggesting utility in studying sensorimotor gating processes. DFMTI is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical neuroscience research. DFMTI is available from various chemical suppliers for research purposes. |
| Molecular Formula |
C20H18F2N4O
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| Molecular Weight |
368.379930973053
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| Exact Mass |
368.144
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| CAS # |
864864-86-8
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| PubChem CID |
15985251
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
545.1±60.0 °C at 760 mmHg
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| Flash Point |
283.5±32.9 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.645
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| LogP |
3
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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 |
27
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| Complexity |
562
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(N=NN1C2=C(C=C(C=C2)F)F)C3=CC4=C(C=C3)C(=O)N(C4)C(C)C
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| InChi Key |
KKZVYGIANGOHBS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H18F2N4O/c1-11(2)25-10-14-8-13(4-6-16(14)20(25)27)19-12(3)26(24-23-19)18-7-5-15(21)9-17(18)22/h4-9,11H,10H2,1-3H3
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| Chemical Name |
5-[1-(2,4-difluorophenyl)-5-methyltriazol-4-yl]-2-propan-2-yl-3H-isoindol-1-one
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| Synonyms |
MK5435; MK5435; MK5435
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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 : ~25 mg/mL (~67.86 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 | 2.7146 mL | 13.5729 mL | 27.1459 mL | |
| 5 mM | 0.5429 mL | 2.7146 mL | 5.4292 mL | |
| 10 mM | 0.2715 mL | 1.3573 mL | 2.7146 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.
mGlu1NAM compounds in the literature.ACS Chem Neurosci.2014 Jul 16;5(7):597-610. |
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Literature mGlu1NAMs exhibit multiple profiles across species in a calcium mobilization assay using cells expressing rat (closed triangles) and human (closed circles) mGlu1.ACS Chem Neurosci.2014 Jul 16;5(7):597-610. |
rmGlu1V757L mutation results in slight decrease in DFMTI NAM activity while hmGlu1L757V mutation gains activity similar to rat WT.ACS Chem Neurosci.2014 Jul 16;5(7):597-610. |
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