| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 250mg | |||
| Other Sizes |
| Targets |
mGlu2 (metabotropic glutamate receptor 2). JNJ-46281222 is a selective and highly potent positive allosteric modulator of mGlu2 with nanomolar affinity (Kd = 1.7 nM) and high modulatory potency (pEC50 = 7.71).
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| ln Vitro |
When mGlu2 WT and CHO-K1 cells were transfected, the mGlu2 receptor mutants F643A and N735D were chosen for the mutant receptor, and binding of JNJ-4628122 to these mutants was dramatically reduced, around ten times less than in WT [1].
JNJ-46281222 binds to mGlu2 with a Kd of 1.7 nM. It shows high modulatory potency with a pEC50 of 7.71. The compound is a selective mGlu2 PAM. Detailed in vitro potency and selectivity profiling has been reported. |
| ln Vivo |
JNJ-46281222 is used to study mGlu2 receptor structure, function, and signaling in vivo. As a PAM, it enhances glutamate-induced mGlu2 activation. Detailed in vivo efficacy in animal models of neurological and psychiatric disorders has been reported.
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| Enzyme Assay |
mGlu2 receptor binding assay: Membranes from cells expressing human mGlu2 are incubated with varying concentrations of JNJ-46281222 and a radiolabeled mGlu2 ligand in binding buffer. Nonspecific binding is determined with excess unlabeled ligand. Bound radioactivity is measured by filtration. Kd values are calculated.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: CHO-K1 Cell Tested Concentrations: Incubation Duration: Experimental Results: The expression of mGlu2 receptor was diminished in mutant cells. Functional PAM assay: Cells expressing mGlu2 and a calcium-sensitive fluorescent dye are treated with JNJ-46281222 at varying concentrations and stimulated with a submaximal concentration of glutamate. Intracellular calcium mobilization is measured by fluorescence. The potentiation of glutamate-induced calcium signaling is quantified, and pEC50 values are calculated. |
| Animal Protocol |
mGlu2 PAM in vivo pharmacology study: Animals are administered JNJ-46281222 via oral or intraperitoneal routes. mGlu2-mediated responses are assessed in behavioral or electrophysiological assays. Target engagement is confirmed by ex vivo receptor occupancy studies.
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| ADME/Pharmacokinetics |
JNJ-46281222 has a molecular weight of 414.47 g/mol and molecular formula C23H25F3N4. CAS number is 1254980-38-5. The compound is a selective mGlu2 PAM with nanomolar affinity. Comprehensive PK parameters have been characterized.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published. JNJ-46281222 is for research use only. Standard laboratory safety practices should be followed when handling this compound. As an mGlu2 PAM, potential effects on central nervous system function should be considered.
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| References | |
| Additional Infomation |
Structure in the first source
JNJ-46281222 is a selective, highly potent positive allosteric modulator of mGlu2 with Kd = 1.7 nM and pEC50 = 7.71. It is used to study mGlu2 receptor structure, function, and signaling. The compound has potential applications in neurological and psychiatric research. No clinical trials or approved上市 status have been reported. |
| Molecular Formula |
C23H25F3N4
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|---|---|
| Molecular Weight |
414.466615438461
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| Exact Mass |
414.203
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| CAS # |
1254980-38-5
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| Related CAS # |
1254980-38-5
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| PubChem CID |
49822115
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
567
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(F)(F)C1C2=NN=C(CC3CC3)N2C=CC=1CN1CCC(C2C=CC=CC=2)CC1
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| InChi Key |
LYDKDODJIBQNLK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H25F3N4/c24-23(25,26)21-19(10-13-30-20(14-16-6-7-16)27-28-22(21)30)15-29-11-8-18(9-12-29)17-4-2-1-3-5-17/h1-5,10,13,16,18H,6-9,11-12,14-15H2
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| Chemical Name |
3-(cyclopropylmethyl)-7-[(4-phenylpiperidin-1-yl)methyl]-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine
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| Synonyms |
JNJ-46281222 JNJ 46281222 JNJ46281222.
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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 : ~62.5 mg/mL (~150.79 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.02 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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 2: ≥ 2.08 mg/mL (5.02 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 20.8 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 | 2.4127 mL | 12.0636 mL | 24.1272 mL | |
| 5 mM | 0.4825 mL | 2.4127 mL | 4.8254 mL | |
| 10 mM | 0.2413 mL | 1.2064 mL | 2.4127 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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