JNJ63955918
JNJ63955918 is a Nav1.7 closed-state blocker (pIC50 = 8.0). JNJ63955918 binds to the resting/closed state of voltage-gated sodium channels, immobilizing the voltage sensor, thereby preventing activation in a low voltage-dependent manner and causing a depolarizing shift in activation without significantly affecting inactivation. JNJ63955918 can be used for pain research.
For research use only. We do not sell to patients.
- Formula: C164H259N47O44S8
- Molecular Weight:3849.62
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
Description
JNJ63955918 is a Nav1.7 closed-state blocker (pIC50 = 8.0). JNJ63955918 binds to the resting/closed state of voltage-gated sodium channels, immobilizing the voltage sensor, thereby preventing activation in a low voltage-dependent manner and causing a depolarizing shift in activation without significantly affecting inactivation. JNJ63955918 can be used for pain research[1][2][3][4][5][6][7][8].
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h Nav1.7 8.0 nM (pIC50) |
Nav1.7 10 nM (IC50) |
h Nav1.7 0.042 μM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
10 nM
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Inhibition of NaV1.7 in HEK293 cells by cell-based assay.
Inhibition of NaV1.7 in HEK293 cells by cell-based assay.
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30813430 |
| HEK293 | IC50 |
3.07 μM
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Inhibition of Nav1.2 in HEK293 cells stably expressing human Nav1.2 assessed by cell-based Nav1.x spiking assay with BeRST1 dye and blue-light test-pulse stimulation after 40 min compound incubation.
Inhibition of Nav1.2 in HEK293 cells stably expressing human Nav1.2 assessed by cell-based Nav1.x spiking assay with BeRST1 dye and blue-light test-pulse stimulation after 40 min compound incubation.
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35860501 |
| HEK293 | IC50 |
6.26 μM
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Inhibition of Nav1.5 in HEK293 cells stably expressing human Nav1.5 assessed by cell-based Nav1.x spiking assay with BeRST1 dye and blue-light test-pulse stimulation after 40 min compound incubation.
Inhibition of Nav1.5 in HEK293 cells stably expressing human Nav1.5 assessed by cell-based Nav1.x spiking assay with BeRST1 dye and blue-light test-pulse stimulation after 40 min compound incubation.
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35860501 |
| HEK293 | IC50 |
0.042 μM
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Inhibition of Nav1.7 in HEK293 cells stably expressing human Nav1.7 assessed by cell-based Nav1.x spiking assay with BeRST1 dye and blue-light test-pulse stimulation after 40 min compound incubation.
Inhibition of Nav1.7 in HEK293 cells stably expressing human Nav1.7 assessed by cell-based Nav1.x spiking assay with BeRST1 dye and blue-light test-pulse stimulation after 40 min compound incubation.
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35860501 |
In Vitro
JNJ63955918 potently inhibits human Nav1.7 in QPatch experiments with a pIC50 of 8.0 and is selective against human Nav1.1, Nav1.2, Nav1.4, Nav1.5, and Nav1.6[1].
JNJ63955918 inhibits human Nav1.7 currents in manual patch-clamp experiments with a pIC50 of 8.0 and modulates Nav1.7 activation and inactivation at 300 nM[1].
JNJ63955918 (300 nM) inhibits most TTX-sensitive currents in rat DRG neurons, but has little effect on TTX-insensitive currents or persistent currents[1].
JNJ63955918 is a closed-state hNaV1.7 inhibitor with an IC50 of approximately 10 nM against hNaV1.7 and an IC50 of approximately 2.5 μM against hNaV1.1, shows lower activity against hNaV1.4 and hNaV1.5, and exhibits higher potency against hNaV1.6 than Tsp1a[2].
JNJ63955918 is a Nav1.7-selective peptide that exhibits 100- to >1000-fold in vitro selectivity over Nav1.1, Nav1.2, Nav1.4, Nav1.5, and Nav1.6[3].
JNJ63955918 is a highly selective NaV1.7 inhibitor with an IC50 of approximately 10 nM in HEK293 cells[6].
JNJ63955918 (40 minutes) is a potent Nav1.7 inhibitor with an IC50 of 0.042 µM, showing > 50-fold selectivity over Nav1.2 and Nav1.5, and a state-dependent ratio of 6.1 in Nav1.x firing HEK293 assays[8].
JNJ63955918 inhibits human Nav1.7 currents in manual patch-clamp experiments with a pIC50 of 8.0 and modulates Nav1.7 activation and inactivation at 300 nM[1].
JNJ63955918 (300 nM) inhibits most TTX-sensitive currents in rat DRG neurons, but has little effect on TTX-insensitive currents or persistent currents[1].
JNJ63955918 is a closed-state hNaV1.7 inhibitor with an IC50 of approximately 10 nM against hNaV1.7 and an IC50 of approximately 2.5 μM against hNaV1.1, shows lower activity against hNaV1.4 and hNaV1.5, and exhibits higher potency against hNaV1.6 than Tsp1a[2].
JNJ63955918 is a Nav1.7-selective peptide that exhibits 100- to >1000-fold in vitro selectivity over Nav1.1, Nav1.2, Nav1.4, Nav1.5, and Nav1.6[3].
JNJ63955918 is a highly selective NaV1.7 inhibitor with an IC50 of approximately 10 nM in HEK293 cells[6].
JNJ63955918 (40 minutes) is a potent Nav1.7 inhibitor with an IC50 of 0.042 µM, showing > 50-fold selectivity over Nav1.2 and Nav1.5, and a state-dependent ratio of 6.1 in Nav1.x firing HEK293 assays[8].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
JNJ63955918 (0.5-2.5 µg/10 µL; intrathecal bolus injection; 15 min-1 h before behavioral testing) produces robust intrathecal analgesia in the rat formalin test, with a phase II pED50 of 6.3[1].
JNJ63955918 (5 µg/10 µL; intrathecal bolus injection; 15 min-1 h before behavioral testing) produces strong and durable hot-plate antinociception and tail-flick antinociception after intrathecal bolus administration in rats[1].
JNJ63955918 (0.5 µg/h; intrathecal infusion; continuous observation for approximately 14 days) maintains thermal antinociception in rats without detectable motor deficits or tolerance[1].
JNJ63955918 (1 µg/10 µL; intrathecal bolus) retains analgesic efficacy in the formalin test in tolerant rats[1].
JNJ63955918 (0.8-2.5 mg/100 µL; perisciatic nerve injection) produces thermal antinociception in the rat Hargreaves paw withdrawal test, with a predominantly ipsilateral effect at lower doses and a bilateral effect at the highest dose[1].
JNJ63955918 (intrathecal) dose-dependently reduces formalin-induced biphasic flinching responses and is equivalent to Ziconotide (HY-P0062) at well-tolerated doses[3].
JNJ63955918 (central and peripheral administration) produces insensitivity to chemical and thermal pain similar to NaV1.7 knockout in animal models, and induces itching[4].
JNJ63955918 (5 µg/10 µL; i.t.; 6 h) induces pain insensitivity in rat thermal and chemical nociception[5].
JNJ63955918 (0.5 µg/h; i.t.; continuous infusion; 14 days) produces analgesic effects in rat tail-flick and hot-plate pain models[5].
JNJ63955918 (5 µg/10 µL; intrathecal bolus injection; 15 min-1 h before behavioral testing) produces strong and durable hot-plate antinociception and tail-flick antinociception after intrathecal bolus administration in rats[1].
JNJ63955918 (0.5 µg/h; intrathecal infusion; continuous observation for approximately 14 days) maintains thermal antinociception in rats without detectable motor deficits or tolerance[1].
JNJ63955918 (1 µg/10 µL; intrathecal bolus) retains analgesic efficacy in the formalin test in tolerant rats[1].
JNJ63955918 (0.8-2.5 mg/100 µL; perisciatic nerve injection) produces thermal antinociception in the rat Hargreaves paw withdrawal test, with a predominantly ipsilateral effect at lower doses and a bilateral effect at the highest dose[1].
JNJ63955918 (intrathecal) dose-dependently reduces formalin-induced biphasic flinching responses and is equivalent to Ziconotide (HY-P0062) at well-tolerated doses[3].
JNJ63955918 (central and peripheral administration) produces insensitivity to chemical and thermal pain similar to NaV1.7 knockout in animal models, and induces itching[4].
JNJ63955918 (5 µg/10 µL; i.t.; 6 h) induces pain insensitivity in rat thermal and chemical nociception[5].
JNJ63955918 (0.5 µg/h; i.t.; continuous infusion; 14 days) produces analgesic effects in rat tail-flick and hot-plate pain models[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (CD; male; 250-300 g)[1]
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Dosage:0.5 µg/10 µL; 2.5 µg/10 µL
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Administration:intrathecal bolus; 15 min-1 h before behavioral testing
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Result:Produced robust intrathecal analgesia in the rat formalin test, with a phase II pED50 of 6.3
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Animal Model:Sprague-Dawley (CD; male; 250-300 g)[1]
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Dosage:5 µg/10 µL
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Administration:intrathecal bolus; 15 min-1 h before behavioral testing
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Result:Produced strong and long-lasting hot-plate antinociception and tail-flick antinociception after intrathecal bolus administration in rats.
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Animal Model:Sprague-Dawley (CD; male; 250-300 g)[1]
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Dosage:0.5 µg/h
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Administration:intrathecal infusion via osmotic pump; continuous; approximately 14 days; followed by approximately 7 days recovery
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Result:At 0.5 µg/h, significant efficacy was maintained for 14 days in both tail-flick and hotplate assays.
Response latencies returned to baseline by day 25.
No motor or other behavioral abnormalities were observed, and treated and vehicle-treated rats gained weight at the same rate.
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Animal Model:Sprague-Dawley (CD; male; 250-300 g)[1]
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Dosage:1 µg/10 µL
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Administration:intrathecal bolus; after approximately 3 h recovery from pump removal; formalin test 1 h later
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Result:In tolerant rats, 1 µg/10 µL significantly reduced phase II formalin flinching to a degree similar to that observed in naïve rats.
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Animal Model:Sprague-Dawley (CD; male; 250-300 g)[1]
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Dosage:0.8 mg/100 µL; 1.4 mg/100 µL; 2.5 mg/100 µL
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Administration:peri-sciatic injection
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Result:At 2.5 mg/100 µL, thermal latencies were maximally elevated on both ipsilateral and contralateral paws for up to 2 h after injection, with no gross motor deficits; latencies returned to normal by 24 h.
At 1.4 mg/100 µL and 0.8 mg/100 µL, thermal latencies were elevated primarily on the ipsilateral side.
In additional animals, 1.4 mg/100 µL produced a significant elevation of the thermal threshold primarily in the ipsilateral limb, lasting 4 h, with a lesser and shorter effect in the contralateral limb; thresholds returned to normal by 24 h.
Chemical Information
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Molecular Weight 3849.62
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Formula C164H259N47O44S8
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Sequence
Gly-Pro-Tyr-Cys-Gln-Lys-Trp-Met-Gln-Thr-Cys-Asp-Ser-Glu-Arg-Lys-Cys-Cys-Glu-Gly-Met-Val-Cys-Arg-Leu-Trp-Cys-Lys-Lys-Lys-Leu-Leu (Disulfide bridge: Cys4-Cys18;Cys11-Cys23;Cys17-Cys27)
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Sequence Shortening
GPYCQKWMQTCDSERKCCEGMVCRLWCKKKLL (Disulfide bridge:Cys4-Cys18;Cys11-Cys23;Cys17-Cys27)
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
Select Batch:
Purity:
99.98%
Assay:
99.98%
ee.:
99.98%
References
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JNJ63955918 Related Classifications
HY-P11045 Related Classifications
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