Nav1.8-IN-25
Nav1.8-IN-25 is a NaV1.8 inhibitor (IC50 of 3.43 μM for resting-state NaV1.8 and IC50 of 3.37 μM for half-inactivated NaV1.8). It exerts analgesic activity in inflammatory, neuropathic, and visceral pain models by blocking voltage-gated Sodium Channel currents in both resting and half-inactivated states. Nav1.8-IN-25 can be used for research on chronic pain.
For research use only. We do not sell to patients.
- Formula: C27H41N5O2
- Molecular Weight:467.65
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
Nav1.8 3.43 μM (IC50, resting-state) |
Nav1.8 3.37 μM (IC50, half-inactivated) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
3.43 μM
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Inhibition of human NaV1.8 currents stably expressed in HEK293 cells measured at the resting state by whole-cell patch-clamp recording with a holding potential of -120 mV and a depolarizing pulse to 0 mV for 40 ms.
Inhibition of human NaV1.8 currents stably expressed in HEK293 cells measured at the resting state by whole-cell patch-clamp recording with a holding potential of -120 mV and a depolarizing pulse to 0 mV for 40 ms.
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42628380 |
| HEK293 | IC50 |
3.37 μM
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Inhibition of human NaV1.8 currents stably expressed in HEK293 cells measured at the half-inactivated state by whole-cell patch-clamp recording with an 8000 ms depolarizing prepulse followed by a return to -120 mV for 30 ms and a test pulse to 0 mV for 40 ms.
Inhibition of human NaV1.8 currents stably expressed in HEK293 cells measured at the half-inactivated state by whole-cell patch-clamp recording with an 8000 ms depolarizing prepulse followed by a return to -120 mV for 30 ms and a test pulse to 0 mV for 40 ms.
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42628380 |
In Vitro
Nav1.8-IN-25 (compound 12d) shows strong binding affinity for NaV1.8 in CMC experiments, with a retention time of 180.0 min[1].
Nav1.8-IN-25 (0.1-10 μM) effectively inhibits NaV1.8 currents in HEK293 cells in a concentration-dependent manner, with IC50 values of 3.43 μM (resting state) and 3.37 μM (half-inactivated state)[1].
Nav1.8-IN-25 (50 mM; 2-60 min) exhibits high in vitro metabolic stability in mouse liver microsomes, with a half-life of 77.85 h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Nav1.8-IN-25 (28.95 μmol/kg; i.p.) exhibits potent analgesic activity against neuropathic pain without inducing tolerance[1].
Nav1.8-IN-25 (28.95 μmol/kg; i.p.) exhibits potent dose-dependent analgesic activity in the Acetic acid (HY-Y0319)-induced visceral pain model[1].
The acute intraperitoneal LD50 of Nav1.8-IN-25 (99.73-200.00 mg/kg; intraperitoneal injection; single injection) is 153.61 mg/kg in mice[1].
Nav1.8-IN-25 (i.p.; single injection) exhibits a favorable safety profile at a dose of 28.944 μmol/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR (6-8 weeks old)[1]
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Dosage:28.95 μmol/kg (equimolar to 3× ED50 of compound 12)
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Administration:i.p.; single dose
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Result:Significantly increased the mechanical withdrawal threshold compared with the vehicle group.
Antinociceptive activity lasted for 300 min after administration.
At equimolar doses, the ΔAUC value was significantly higher than that of the lead compound 12.
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Animal Model:ICR (6-8 weeks old)[1]
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Dosage:28.95 μmol/kg (equimolar to 3× ED50 of compound 12)
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Administration:i.p.; single dose
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Result:Both the mechanical withdrawal threshold and the AUC values were markedly higher than those in the vehicle group.
The analgesic effect at the peak time point showed no obvious attenuation compared with the initial administration on days 8, 10, 12, and 14.
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Animal Model:ICR (6-8 weeks old)[1]
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Dosage:28.95 μmol/kg (equimolar to 3× ED50 of compound 12)
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Administration:i.p.; single dose
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Result:Significantly reduced the number of writhing responses following intraperitoneal injection of acetic acid.
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Animal Model:C57BL/6J wild-type and SCN10A knockout (NaV1.8−/−) (6-8 weeks old)[1]
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Dosage:28.95 μmol/kg (equimolar to 3× ED50 of compound 12)
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Administration:i.p.; single dose
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Result:The analgesic activity was nearly abolished in NaV1.8−/− mice compared with that in WT mice.
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Animal Model:ICR (6-8 weeks old)[1]
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Dosage:Analgesic dose (single administration)
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Administration:i.p.; single dose
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Result:Showed no significant changes in ALT, LDH, α-HBDH, CREA, or UREA levels.
No apparent tissue damage or morphological alteration was observed in major organs (heart, liver, and kidney) according to H&E staining.
A statistically significant increase in serum AST level was observed after administration.
The LD50 was calculated to be 165.96 mg/kg, with TI > 10.
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Animal Model:Mice (strain not specified)[1]
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Dosage:99.73, 118.68, 141.23, 168.06, 200.00 mg/kg
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Administration:i.p.; single injection
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Result:Determined the LD50 of compound 12d to be 153.61 mg/kg via the Bliss method.
Observed mortality at doses from 141.23 mg/kg to 200.00 mg/kg.
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Animal Model:Mice (strain not specified)[1]
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Dosage:28.944 μmol/kg
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Administration:i.p.; single injection
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Result:Reported no significant changes in biochemical parameters in blood samples at 24 h post-dose compared to the vehicle group.
Showed no observable toxicity in representative H&E-stained sections of major organs (liver, kidney, heart).
Chemical Information
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Molecular Weight 467.65
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Formula C27H41N5O2
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SMILES
CCCN1C2=C(C=NN(CC(N(CCN)CCCC(C)CC(C)(C)C)=O)C2=O)C3=CC=CC=C31
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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
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Nav1.8-IN-25 Related Classifications
HY-189273 Related Classifications
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