| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 1g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
JNJ-37822681 targets the dopamine D₂ receptor. It acts as a potent and specific antagonist, binding to the receptor and blocking the action of dopamine. Its unique feature is its fast dissociation rate, meaning it does not stay bound to the receptor for a long time. This kinetic profile is believed to be responsible for its favorable side-effect profile compared to other antipsychotics. The compound shows no significant affinity for other receptors like α1, α2, H1, muscarinic, D1, D3, 5-HT2A, or 5-HT2C.
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|---|---|
| ln Vitro |
In vitro, JNJ-37822681 has been characterized by its high affinity and selectivity for the dopamine D₂ receptor. It exhibits a Ki of 158 nM for the D₂ receptor. In functional assays, it acts as an antagonist, inhibiting dopamine-mediated signaling. Its rapid dissociation kinetics have been demonstrated in binding studies, distinguishing it from other D₂ antagonists.
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| ln Vivo |
In vivo, JNJ-37822681 is a centrally active compound with optimal brain disposition. Animal studies have shown that it can occupy D₂ receptors in the brain and reverse behavioral effects induced by dopamine agonists, consistent with antipsychotic activity. Its fast-dissociating properties are reflected in its in vivo receptor occupancy profile, which is expected to translate into a lower risk of motor side effects.
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| Enzyme Assay |
In vitro enzyme or receptor binding (non-cell) assays for JNJ-37822681 are used to determine its affinity for the dopamine D₂ receptor. These assays involve incubating a membrane preparation from cells expressing the human D₂ receptor with a radiolabeled ligand, such as [³H]spiperone. JNJ-37822681 is added at varying concentrations to compete with the radioligand, and the amount of bound radioactivity is measured to calculate the Ki. Selectivity is confirmed by testing against a panel of other receptors.
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| Cell Assay |
In vitro cell-based assays for JNJ-37822681 involve measuring its functional activity as an antagonist. Cells expressing the D₂ receptor are treated with a D₂ agonist (e.g., quinpirole) to stimulate downstream signaling, such as inhibition of cAMP accumulation. The ability of JNJ-37822681 to reverse this inhibition and restore cAMP levels is measured to quantify its antagonist potency.
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| Animal Protocol |
In vivo animal experiments for JNJ-37822681 are conducted using rodent models of psychosis. The compound is administered, and its ability to block apomorphine-induced climbing behavior or conditioned avoidance response is measured. Receptor occupancy in the brain is assessed using ex vivo radioligand binding or positron emission tomography (PET) imaging. The compound's potential for extrapyramidal side effects is evaluated using catalepsy tests.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of JNJ-37822681 indicate it is centrally active with optimal brain disposition. The compound has a molecular weight of 388.33 and a formula of C₁₇H₁₇F₅N₄. It is orally bioavailable and able to cross the blood-brain barrier, achieving sufficient concentrations in the brain to occupy D₂ receptors. Its rapid dissociation kinetics are a key feature of its overall pharmacological profile.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for JNJ-37822681 are primarily derived from preclinical studies. As a D₂ antagonist, its safety profile is compared to other antipsychotics. Its fast-dissociating property is expected to result in a lower incidence of extrapyramidal symptoms and hyperprolactinemia compared to typical antipsychotics. However, as with all D₂ antagonists, there may be risks of sedation, weight gain, and metabolic changes.
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| References |
Alves IL, Willemsen AT, Dierckx RA, da Silva AM, Koole M. Dual time-point imaging for post-dose binding potential estimation applied to a [11C]raclopride PET dose occupancy study. J Cereb Blood Flow Metab. 2016 Apr 12. pii: 0271678X16644463. [Epub ahead of print] PubMed PMID: 27073203.
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| Additional Infomation |
JNJ-37822681 has been used in trials investigating the treatment of schizophrenia.
Other information: JNJ-37822681 is being developed as a potential treatment for schizophrenia. Its unique fast-dissociating profile makes it a promising candidate for an antipsychotic with a better side-effect profile. The compound is available for research purposes from various chemical suppliers. |
| Molecular Formula |
C17H17F5N4
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|---|---|
| Molecular Weight |
372.33568
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| Exact Mass |
444.091
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| CAS # |
935776-74-2
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| PubChem CID |
16058752
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.813
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
441
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C(F)=CC(CN2CCC(NC3C=CC(C(F)(F)F)=NN=3)CC2)=CC=1
|
| InChi Key |
UVUYWJWYRLJHEN-UHFFFAOYSA-N
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| InChi Code |
1S/C17H17F5N4/c18-13-2-1-11(9-14(13)19)10-26-7-5-12(6-8-26)23-16-4-3-15(24-25-16)17(20,21)22/h1-4,9,12H,5-8,10H2,(H,23,25)
|
| Chemical Name |
3-Pyridazinamine, N-(1-((3,4-difluorophenyl)methyl)-4-piperidinyl)-6-(trifluoromethyl)-
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| Synonyms |
JNJ-37822681 JNJ 37822681 JNJ37822681.
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.6857 mL | 13.4286 mL | 26.8572 mL | |
| 5 mM | 0.5371 mL | 2.6857 mL | 5.3714 mL | |
| 10 mM | 0.2686 mL | 1.3429 mL | 2.6857 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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