| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
JNJ-42226314 targets monoacylglycerol lipase (MAGL), a key enzyme in endocannabinoid metabolism that hydrolyzes 2-arachidonoylglycerol (2-AG). By inhibiting MAGL with an IC50 of 10 nM, the compound increases 2-AG levels, enhancing endocannabinoid signaling. It is selective for MAGL over a panel of 15 serine proteases at 10 µM.
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| ln Vitro |
JNJ-42226314's IC50 values against mouse brain, rat brain, human PBMC, and human HeLa cells are 1.13 nM, 1.88 nM, 0.67 nM, and 0.97 nM, respectively [1].
In vitro, JNJ-42226314 potently inhibits MAGL with an IC50 of 10 nM. It is a competitive, highly selective, and reversible non-covalent inhibitor. The compound enhances 2-AG levels, leading to increased endocannabinoid signaling. Its selectivity for MAGL over other serine proteases has been demonstrated. |
| ln Vivo |
In vivo, JNJ-42226314 (ip; 3 mg/kg and 30 mg/kg; 120 minutes) elevates hippocampus 2-AG in a dose-dependent manner [1]. When JNJ-42226314 (ip; 30 mg/kg) was administered, total arousal time increased by up to 8 hours as opposed to just 2 hours [1]. The rat complete Freund's adjuvant (CFA) inflammatory pain model exhibits analgesic effects in response to intraperitoneal injection of JNJ-42226314 (30 mg/kg) [1]. JNJ-42226314's MAGL t1/2 values in rats, mice, and humans are 27.2, 27.6, and 11.4 minutes, respectively [1].
In vivo, JNJ-42226314 exhibits antinociceptive efficacy in models of neuropathic and inflammatory pain via endogenous cannabinoid 2-arachidonoylglycerol (2-AG). It also shows anti-injury effects. As a MAGL inhibitor, it can be administered to animal models of pain, inflammation, and other conditions. Its ability to enhance 2-AG signaling translates to in vivo efficacy. |
| Enzyme Assay |
In vitro enzyme assays for JNJ-42226314 involve measuring its inhibition of MAGL activity. Recombinant MAGL is incubated with increasing concentrations of the compound and a fluorogenic substrate (e.g., 7-hydroxycoumarin arachidonate) in assay buffer. The release of the fluorophore is measured fluorometrically. IC50 values are calculated from dose-response curves. Selectivity is confirmed by testing against a panel of serine proteases.
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| Cell Assay |
For in vitro cell-based assays, cells are cultured and treated with JNJ-42226314 at various concentrations. MAGL inhibition is confirmed by measuring 2-AG levels in cell lysates or supernatants using LC-MS. The compound's effects on endocannabinoid signaling are assessed by measuring downstream signaling pathways. Cell viability is assessed by standard assays.
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| Animal Protocol |
Animal/Disease Models: Male C57Bl/6 mice weighing 20-30g and male SD (SD (Sprague-Dawley)) rats weighing 300-400g [1]
Doses: 3mg/kg and 30mg/kg Route of Administration: ip; 120 minutes Experimental Results: Hippocampus in vivo 2-AG increased in a dose-dependent manner. In vivo animal studies with JNJ-42226314 are conducted in models of neuropathic and inflammatory pain. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Pain responses are assessed using behavioral tests such as von Frey filaments or hot plate tests. The compound's antinociceptive efficacy has been demonstrated. |
| ADME/Pharmacokinetics |
JNJ-42226314 (CAS: 1252765-13-1) has a molecular weight of 489.56 g/mol and a molecular formula of C26H24FN5O2S. Chemical name: 1-(4-fluorophenyl)-5-{3-[4-(1,3-thiazole-2-carbonyl)piperazin-1-yl]azetidine-1-carbonyl}-1H-indole. Appearance: solid powder. Purity: ≥98%. Storage: -20°C. The compound is a highly selective MAGL inhibitor.
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| Toxicity/Toxicokinetics |
JNJ-42226314 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a MAGL inhibitor, it enhances endocannabinoid signaling, which may have effects on pain, mood, and inflammation. The compound's selectivity for MAGL over other serine proteases may reduce off-target effects. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
JNJ-42226314 is a competitive, highly selective, and reversible non-covalent inhibitor of monoacylglycerol lipase (MAGL) with an IC50 of 10 nM. It enhances 2-AG levels and exhibits antinociceptive efficacy in models of neuropathic and inflammatory pain. It has a molecular weight of 489.56 g/mol and a molecular formula of C26H24FN5O2S. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C26H24FN5O2S
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|---|---|
| Molecular Weight |
489.5645
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| Exact Mass |
489.163
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| CAS # |
1252765-13-1
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| PubChem CID |
59625954
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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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 |
4
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| Heavy Atom Count |
35
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| Complexity |
782
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C([H])=C([H])N=C1C(N1C([H])([H])C([H])([H])N(C([H])([H])C1([H])[H])C1([H])C([H])([H])N(C(C2C([H])=C([H])C3=C(C([H])=C([H])N3C3C([H])=C([H])C(=C([H])C=3[H])F)C=2[H])=O)C1([H])[H])=O
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| InChi Key |
IVOACCSOISMVBL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H24FN5O2S/c27-20-2-4-21(5-3-20)32-9-7-18-15-19(1-6-23(18)32)25(33)31-16-22(17-31)29-10-12-30(13-11-29)26(34)24-28-8-14-35-24/h1-9,14-15,22H,10-13,16-17H2
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| Chemical Name |
[1-(4-fluorophenyl)indol-5-yl]-[3-[4-(1,3-thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone
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| Synonyms |
JNJ-42226314 JNJ 42226314
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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 : ~250 mg/mL (~510.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (12.77 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 62.5 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: ≥ 6.25 mg/mL (12.77 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 62.5 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. View More
Solubility in Formulation 3: ≥ 6.25 mg/mL (12.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0427 mL | 10.2133 mL | 20.4265 mL | |
| 5 mM | 0.4085 mL | 2.0427 mL | 4.0853 mL | |
| 10 mM | 0.2043 mL | 1.0213 mL | 2.0427 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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