JNJ-47965567 |
| رقم الكتالوجGC43931 |
JNJ-47965567 هو مضاد P2X7 قابل للاختراق مركزيًا ، عالي التقارب ، انتقائي ، مع pKis 7.9 و 8.7 للإنسان والجرذان P2X7 ، على التوالي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1428327-31-4
Sample solution is provided at 25 µL, 10mM.
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JNJ-47965567 is a centrally permeable, high affinity, selective P2X7 antagonist with IC50 values of 5nM and 10nM for human and mouse P2X7 receptors, respectively[1]. The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel that senses high extracellular ATP concentrations and has been considered a target for the treatment of neuroinflammatory and neurodegenerative diseases[2]. JNJ-47965567 can be used to study the role of P2X7 in central nervous system pathophysiological models[3].
In vitro, JNJ-47965567 (1µM) pre-treated human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs) for 30min showed an inhibitory effect on cell viability at low concentrations of BzATP, but its effect was completely inhibited under the strong toxic conditions induced by high concentrations of BzATP[4].
In vivo, JNJ-47965567 (30mg/kg) was able to increase the seizure threshold in rats with a fully kindled model by subcutaneous injection, and its combination with carbamazepine significantly enhanced the anticonvulsant effect[1]. JNJ-47965567 (30mg/kg) was significantly attenuated by subcutaneous injection in SD rats by amphetamine-induced hyperactivity[5]. JNJ-47965567 (30mg/kg) was treated by intraperitoneal injection in female SOD1G93A mice, which reduced the body weight of mice and improved motor coordination and phenotypic scores[6].
References:
[1] Fischer W, Franke H, Krügel U, et al. Critical evaluation of P2X7 receptor antagonists in selected seizure models[J]. PLoS One, 2016, 11(6): e0156468.
[2] Zheng H, Liu Q, Zhou S, et al. Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases[J]. Frontiers in Immunology, 2024, 15: 1345625.
[3] Bhattacharya A. Recent advances in CNS P2X7 physiology and pharmacology: focus on neuropsychiatric disorders[J]. Frontiers in Pharmacology, 2018, 9: 30.
[4] Francistiová L, Vörös K, Lovász Z, et al. Detection and functional evaluation of the P2X7 receptor in hiPSC derived neurons and microglia-like cells[J]. Frontiers in Molecular Neuroscience, 2022, 14: 793769.
[5] Bhattacharya A, Wang Q, Ao H, et al. Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ‐47965567[J]. British journal of pharmacology, 2013, 170(3): 624-640.
[6] Ruiz-Ruiz C, García-Magro N, Negredo P, et al. Chronic administration of P2X7 receptor antagonist JNJ-47965567 delays disease onset and progression, and improves motor performance in ALS SOD1G93A female mice[J]. Disease Models & Mechanisms, 2020, 13(10): dmm045732.
| Cell experiment [1]: | |
Cell lines | Neural progenitor cells (NPCs) |
Preparation Method | Control hiPSC-derived Neural progenitor cells (NPCs) were cultured on 96-well plates at 90,000 cells/cm2 density and treated with different concentrations of ATP and BzATP and incubated at standard cultivation conditions for 24h. Cells were pretreated with 1µM JNJ-47965567 for 30min. Viability of the cultures was assessed using PrestoBlueTM Cell Viability Reagent. |
Reaction Conditions | 1µM; 30min |
Applications | The viability of the cells treated with lower concentrations of BzATP was not different from the untreated control, but the JNJ-47965567 pre-treated cells showed decreased viability. The viability of the cells treated with higher concentrations of BzATP was significantly decreased, and pre-treatment with JNJ-47965567 had no effect on the measured viability. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | On day 1 of the experiment, animals were acclimated to the procedure room for at least 1 hour and then each cage was placed onto a MotorMonitor rack, which surrounded each animal cage by a grid of photobeams (7 beams along the width of the cage and 15 beams along the length). The photobeams allowed for tracking the distance traveled by each animal. After 1h, rats were injected subcutaneously with either vehicle (30% sulfobutylether beta-cyclodextrin) or JNJ-47965567 (30mg/kg) and locomotor activity was recorded for an additional hour. All animals then received an injection of d-amphetamine sulfate (2mg/kg, i.p.) and locomotor activity was recorded for 2 additional hours. On day 2-5, the The experiment was repeated in the same manner, with the same treatments provided each day. After 2 days of drug-withdrawal, the same procedure was repeated again on day 8 with another amphetamine challenge. |
Dosage form | 30mg/kg; s.c. |
Applications | JNJ-47965567 show significant effect on attenuating the sensitization of amphetamine induced locomotion. |
References: | |
| Cas No. | 1428327-31-4 | SDF | |
| Canonical SMILES | O=C(C1=CC=CN=C1SC2=CC=CC=C2)NCC3(CCOCC3)N(CC4)CCN4C5=CC=CC=C5 | ||
| Formula | C28H32N4O2S | M.Wt | 488.6 |
| الذوبان | DMF: 30 mg/mL,DMSO: 30 mg/mL,DMSO:PBS(pH 7.2) (1:3): 0.25 mg/mL,Ethanol: 12.5 mg/mL | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0467 mL | 10.2333 mL | 20.4666 mL |
| 5 mM | 0.4093 mL | 2.0467 mL | 4.0933 mL |
| 10 mM | 0.2047 mL | 1.0233 mL | 2.0467 mL |
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)
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