| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
mGlu1 ( Ki = 2.5 nM )
FITM targets the mGlu1 receptor (mGluR1), a class C G protein-coupled receptor that mediates slow excitatory neurotransmission in the central nervous system. As a negative allosteric modulator, FITM binds to a site distinct from the orthosteric glutamate binding site, reducing the receptor's response to glutamate without directly competing with the endogenous ligand. It has a Ki of 2.5 nM. |
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| ln Vitro |
FITM slides into the long, narrow pocket with precision. Most of the ligand-receptor interactions are hydrophobic with the exception of the contacts of the pyrimidine-amine group with the T815 7.38 side chain. The mGlu1 binding pocket for FITM largely corresponds to mutagenic data for the common allosteric site in mGlus and likely extends to other class C GPCRs. FITM, which exhibits superior selectivity and affinity for mGlu1 over mGlu5[1]. During molecular dynamics simulations, FITM has a high hydrogen bond occupancy with Tyr805 and Thr815 in dimers A and B of mGlu1. Dynamic hydrogen bonds are formed by the nitrogen and hydrogen atoms of FITM with the oxygen and hydrogen atoms of Thr815 and Tyr805, respectively. It suggests that FITM and allosteric sites interact strongly through attraction[2].
FITM potently inhibits mGlu1 receptor activity with a Ki of 2.5 nM. It shows high selectivity for mGlu1 over other mGlu receptors, with IC₅₀ values >10 µM for mGlu5 and mGlu8. This selectivity makes FITM a valuable tool for dissecting the specific roles of mGlu1 in physiological and pathological processes. |
| ln Vivo |
The input function is unaffected by the pretreatment of rats with unlabeled FITM (1 mg/kg), which occupies more than 99% of the mGluR1 binding site of 18F-FITM. The Kd (nM) and Bmax (pmol/mL) obtained by the Scatchard analyses with the multidose ligand assays are 2.1 and 36.3, respectively, for the thalamus; 2.1 and 27.5, respectively, for the hippocampus; 1.5 and 22.2, respectively, for the striatum; and 1.5 and 20.5, respectively, for the cingulate cortex with a high confidence[3]. 18F-FITM shows excellent pharmacokinetics, namely the dense and specific accumulation in mGlu1-positive melanomas versus mGlu1-negative hepatoma and normal tissues. In addition, levels of mGlu1 protein expression in melanomas and melanoma metastases were correlated with the accumulation levels of radioactivity[4].
FITM demonstrates in vivo activity in rodent models. At a dose of 0.3 mg/kg, it decreases methamphetamine-induced hyperlocomotion in mice. At a dose of 1 mg/kg, it reverses disruptions in prepulse inhibition induced by methamphetamine and ketamine in rats. These effects suggest that mGlu1 modulation may have therapeutic potential in psychiatric disorders involving dopaminergic and glutamatergic dysfunction. |
| Enzyme Assay |
For non-cellular receptor binding assays, FITM's affinity for mGlu1 can be evaluated using radioligand binding studies. Membrane preparations from cells expressing mGlu1 are incubated with a radiolabeled mGlu1 ligand (e.g., [³H]FITM or a related compound) and varying concentrations of unlabeled FITM. Binding displacement curves are generated to determine the Ki value.
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| Cell Assay |
In vitro cellular assays for FITM involve treating cells expressing mGlu1 with the compound and measuring receptor-mediated signaling. Functional assays typically measure intracellular calcium mobilization, as mGlu1 is coupled to Gq proteins. Cells are loaded with a calcium-sensitive dye (e.g., Fluo-4) and stimulated with glutamate in the presence of varying concentrations of FITM. The reduction in calcium response is quantified to determine the IC₅₀.
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| Animal Protocol |
Rats: Different doses of unlabeled FITM (0, 1, 5, or 30 μg/kg or 1 mg/kg) are administered to Sprague-Dawley rats prior to a bolus injection of 18F-FITM (17–18 MBq, 30–40 pmol, 0.1 mL). Acquired were estimates of the equilibrium state and BPND [3].
In vivo animal experiments with FITM involve intraperitoneal or oral administration to rodents. Behavioral assays such as locomotor activity and prepulse inhibition are used to assess the effects of mGlu1 modulation on behavior. The compound's effects on methamphetamine-induced hyperlocomotion and ketamine-induced disruptions in prepulse inhibition are evaluated. Pharmacokinetic studies are conducted to determine exposure levels. |
| ADME/Pharmacokinetics |
FITM has a molecular weight of 371.43 and a molecular formula of C₁₈H₁₈FN₅OS. It is a solid at room temperature and is typically stored at -20°C. Purity is ≥98%. The compound is soluble in DMSO and other organic solvents. It is stable under recommended storage conditions and is protected from light and moisture.
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| Toxicity/Toxicokinetics |
Toxicological data for FITM are limited as it is a research compound. In preclinical studies, it has been generally well-tolerated at the doses used for behavioral experiments. Standard laboratory safety precautions should be followed when handling the compound. It may cause skin, eye, and respiratory irritation.
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| References |
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| Additional Infomation |
A PET ligand for mGluR1 receptor imaging; structure described in the first article.
FITM is a potent and selective negative allosteric modulator of mGlu1. It is used as a research tool to study the role of mGlu1 in neurological and psychiatric disorders. The compound's high selectivity for mGlu1 over other mGlu receptors makes it valuable for target validation studies. It is available from various commercial suppliers for research applications. |
| Molecular Formula |
C18H18FN5OS
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|---|---|
| Molecular Weight |
371.4318
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| Exact Mass |
371.12
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| Elemental Analysis |
C, 58.21; H, 4.88; F, 5.11; N, 18.86; O, 4.31; S, 8.63
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| CAS # |
932737-65-0
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| PubChem CID |
16660135
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| Appearance |
White to off-white solid powder
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| Melting Point |
174 °C
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| LogP |
1.45
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
475
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N(C)C1SC=C(C2C=C(NC(C)C)N=CN=2)N=1)C1C=CC(F)=CC=1
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| InChi Key |
WIVGIKIKQHUFOD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H18FN5OS/c1-11(2)22-16-8-14(20-10-21-16)15-9-26-18(23-15)24(3)17(25)12-4-6-13(19)7-5-12/h4-11H,1-3H3,(H,20,21,22)
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| Chemical Name |
4-fluoro-N-methyl-N-[4-[6-(propan-2-ylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]benzamide
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| Synonyms |
FITM
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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: ~100 mg/mL (~269.2 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.73 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 (6.73 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 | 2.6923 mL | 13.4615 mL | 26.9230 mL | |
| 5 mM | 0.5385 mL | 2.6923 mL | 5.3846 mL | |
| 10 mM | 0.2692 mL | 1.3461 mL | 2.6923 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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