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Purity: ≥98%
JNJ-47965567 is a novel, potent, centrally permeable, high affinity and selective antagonist of the purinergic receptor P2X subtype 7 (P2X7), which is a ligand-gated ion channel. An increasing body of evidence suggests that the purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7) in the CNS may play a key role in neuropsychiatry, neurodegeneration and chronic pain. JNJ-47965567 is potent high affinity (pKi 7.9 ± 0.07), selective human P2X7 antagonist, with no significant observed speciation. In native systems, the potency of the compound to attenuate IL-1β release was 6.7 ± 0.07 (human blood), 7.5 ± 0.07 (human monocytes) and 7.1 ± 0.1 (rat microglia). JNJ-47965567 exhibited target engagement in rat brain, with a brain EC50 of 78 ± 19 ng·mL(-1) (P2X7 receptor autoradiography) and functional block of Bz-ATP induced IL-1β release. JNJ-47965567 (30 mg·kg(-1) ) attenuated amphetamine-induced hyperactivity and exhibited modest, yet significant efficacy in the rat model of neuropathic pain. No efficacy was observed in forced swim test.
| ln Vitro |
High affinity for human and transporter P2X7 is demonstrated by JNJ-47965567 in 1321N1 cell membrane preparations [1]. When treated with LPS and BZ-ATP, JNJ-47965567 relaxes the release of IL-1β; the pIC50s are 6.7±0.07 (human blood) and 7.5±0.07 (blood sample), respectively. Under the same conditions, JNJ-47965567 does not prevent the release of IL-6 and TNF-α. (statistical small cells) and 7.1±0.1 (human monocytes) [1]. 】.
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| ln Vivo |
JNJ-47965567 (30-100 mg/kg; sc) fragments the release of IL-1β caused by Bz-ATP [1]. JNJ-47965567 (30 mg/kg) links neuropathic pain models and isolates amphetamine-induced hyperactivity.
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| Animal Protocol |
Animal/Disease Models: Male Sprague Dawley rat [1]
Doses: 30 mg/kg, 100 mg/kg Route of Administration: subcutaneous injection ; shows habitual but significant efficacy [1]. Results 30 minutes before Bz-ATP infusion: The 100 mg/kg dose group Dramatically attenuated IL-1β release, while the 30 mg/kg dose group had no effect. |
| References |
| Molecular Formula |
C28H32N4O2S
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|---|---|
| Molecular Weight |
488.644285202026
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| Exact Mass |
488.224
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| CAS # |
1428327-31-4
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| PubChem CID |
66553218
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
690.1±55.0 °C at 760 mmHg
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| Flash Point |
371.2±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.670
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| LogP |
6.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
653
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XREFXUCWSYMIOG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H32N4O2S/c33-26(25-12-7-15-29-27(25)35-24-10-5-2-6-11-24)30-22-28(13-20-34-21-14-28)32-18-16-31(17-19-32)23-8-3-1-4-9-23/h1-12,15H,13-14,16-22H2,(H,30,33)
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| Chemical Name |
N-[[4-(4-phenylpiperazin-1-yl)oxan-4-yl]methyl]-2-phenylsulfanylpyridine-3-carboxamide
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| Synonyms |
JNJ-47965567; JNJ 47965567; JNJ47965567.
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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 (~204.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.12 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 (5.12 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 25.0 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: ≥ 2.5 mg/mL (5.12 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 | 2.0465 mL | 10.2325 mL | 20.4650 mL | |
| 5 mM | 0.4093 mL | 2.0465 mL | 4.0930 mL | |
| 10 mM | 0.2046 mL | 1.0232 mL | 2.0465 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.
 Displacement of [3H] A-804598 byJNJ-47965567, A-804598, A-438079 and AZ-10606120 in membrane preparations of 1321N1 cells expressing either the recombinant human (upper panel) or rat (lower panel) isoform. |
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 Attenuation of IL-1β release in human blood and human monocytes (PBMC) byJNJ-47965567.Br J Pharmacol.2013 Oct;170(3):624-40. |
 Effect of P2X7 antagonists on net IL-1β release in primary cultures of rat microglia (upper panel) or on calcium flux in rat astrocytes (lower panel).Br J Pharmacol.2013 Oct;170(3):624-40. |
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