Nav1.8-IN-26
Nav1.8-IN-26 is an orally active NaV1.8 inhibitor (IC50 = 3.0 nM). Nav1.8-IN-26 exhibits selectivity over other sodium channel subtypes, while inhibiting the hERG potassium channel (IC50 = 16 μM), and produces analgesic effects in rat pain models. Nav1.8-IN-26 can be used for research on postoperative pain and inflammatory pain.
For research use only. We do not sell to patients.
- CAS No.: 3115361-08-2
- Formula: C24H21DF8N2O5
- Molecular Weight:571.44
-
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]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
Nav1.8 3.0 nM nM (IC50) |
hERG 16 μM (IC50) |
In Vitro
Nav1.8-IN-26 (0.16-40 μM; 1-3 min each time) weakly inhibits hERG channels in hERG-CHO cells, with an IC50 of 16 μM[1].
Nav1.8-IN-26 (0.1-10 μM) does not significantly induce CYP1A2 in HU8409 primary human hepatocytes, but induces CYP2B6 and CYP3A4[1].
Nav1.8-IN-26 (10-30 μM) inhibits CYP2C8, CYP2C9, and CYP3A4/5 (6β-hydroxytestosterone) in human liver microsomes, with estimated IC50 values below 30 μM[1].
Nav1.8-IN-26 shows good in vitro metabolic stability in human, monkey, dog, rat, and mouse liver microsomes, with intrinsic clearance values ranging from 5.48 to 33.3 mL/min/kg[1].
Nav1.8-IN-26 (10 μM; 5 hours) is highly bound to rat plasma proteins, with a plasma protein binding rate of 98.62%[1].
Nav1.8-IN-26 (1-1000 μg/well) is negative in the Mini-Ames test against Salmonella typhimurium strains TA98 and TA100 under S9 and non-S9 conditions[1].
Nav1.8-IN-26 (1-50 μg/mL (S9 activation); 0.5-25 μg/mL (non-S9); 4 hours (S9 activation); 24 hours (non-S9)) is negative in the micronucleus test in CHL cells[1].
Nav1.8-IN-26 (10-100 μM; 24 h) shows no cytotoxicity in CHO−K1 and HepG2 cells at concentrations up to 30 μM[1].
Nav1.8-IN-26 (24 hours at 37 °C) has an equilibrium aqueous solubility of 34.9 µM (19.9 µg/mL) at pH 7.4[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:CHO−K1 and HepG2 cells
-
Concentration:10, 30, 100 μM
-
Incubation Time:24 h
-
Result:Showed no cytotoxicity in CHO−K1 or HepG2 cells at concentrations up to 30 μM.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | MRT | CL | AUC0-∞ | F | MRT0-∞ | Vss |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dog[1] | 5 mg/kg | p.o. | 2.93 h | 0.83 h | 707 ng/mL | 5385 ng/mL·h | 5.39 h | / | / | 27 % | / | / |
| Dog[1] | 80 mg/kg | p.o. | 2.20 h | 4.0 h | 10,100 ng/mL | 91,200 ng/mL·h | 6.45 h | / | / | 28 % | / | / |
| Dog[1] | 1 mg/kg | i.v. | 3.46 h | / | 2700 ng/mL | 3984 ng/mL·h | 2.87 h | 4.21 mL/min/kg | / | / | / | / |
| Dog[1] | 5 mg/kg | p.o. | 6.94 h | 2.0 h | 2390 ng/mL | 29,100 ng/mL·h | 9.82 h | / | / | / | / | / |
| Dog[1] | 30 mg/kg | p.o. | 8.38 h | 4.0 h | 8000 ng/mL | 134,000 ng/mL·h | 12.80 h | / | / | / | / | / |
| Cynomolgus Monkey[1] | 20 mg/kg | p.o. | 4.26 h | 4.0 h | 1280 ng/mL | 87,900 ng/mL·h | 6.86 h | / | / | / | / | / |
| Rat[1] | 1 mg/kg | i.v. | 3.46 h | / | 2700 ng/mL | 3984 ng·h/mL | / | 4.21 mL/min/kg | 4044 ng·h/mL | / | 2.87 h | 0.71 L/kg |
| Rat[1] | 5 mg/kg | p.o. | 2.93 h | 0.83 h | 707 ng/mL | 5385 ng·h/mL | / | / | 5409 ng·h/mL | / | 5.39 h | / |
| Rat[1] | 80 mg/kg | p.o. | 2.20 h | 4 h | 10100 ng/mL | 91.2 μg·h/mL | 6.45 h | / | 91.3 μg·h/mL | / | / | / |
| Dog[1] | 30 mg/kg | p.o. | 8.38 h | 4 h | 8000 ng/mL | 134 μg·h/mL | 12.8 h | / | 137 μg·h/mL | / | / | / |
| Dog[1] | 20 mg/kg | p.o. | 4.26 h | 4 h | 1280 ng/mL | 8.79 μg·h/mL | 6.86 h | / | 9.00 μg·h/mL | / | / | / |
In Vivo
Nav1.8-IN-26 (30 mg/kg; p.o.; single administration) produces potent analgesic effects in the rat CFA-induced inflammatory pain model[1].
Nav1.8-IN-26 (10-30 mg/kg) produces antinociceptive efficacy in a rat postoperative pain model, with %MPE values of 31.26% and 38.65% at 10 and 30 mg/kg, respectively[1].
Nav1.8-IN-26 (10-30 mg/kg) produces efficacy in the rat CFA-induced inflammatory pain model, with a %MPE of 24.40% at 30 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Sprague-Dawley (SD) (male, 220 g)[1]
-
Dosage:10 mg/kg
-
Administration:p.o.; single administration
-
Result:At 10 mg/kg, produced better analgesic performance than VX-548, with higher paw withdrawal threshold values across the observation period.
Displayed clear dose-dependent analgesic effects.
Peak analgesic action appeared at 4 h after administration.
The anti-nociceptive effect AUC was further analyzed to assess in vivo efficacy.
At 10 mg/kg, yielded a higher pain tolerance AUC than VX-548.
The in vivo efficacy increased in a dose-dependent manner.
%MPE reached 31.26% at 10 mg/kg.
This value was approximately twice the level of VX-548.
-
Animal Model:Sprague-Dawley (SD) (male, 220 g)[1]
-
Dosage:10 mg/kg and 30 mg/kg
-
Administration:p.o.; single administration
-
Result:At 10 mg/kg, no significant efficacy was observed.
Demonstrated robust analgesia at 30 mg/kg, with a peak effect at approximately 4 h post-administration.
Specifically, at this dose, the MPE % was about 12-fold higher than that of VX-548, indicating superior efficacy in this inflammatory pain model.
Application
1. This compound can be used as a tracer
2. This compound can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS.
Chemical Information
-
CAS No. 3115361-08-2
-
Unlabeled CAS 3115361-10-6
-
Molecular Weight 571.44
-
Formula C24H21DF8N2O5
-
SMILES
C[C@H]1[C@H]([C@@H](O[C@@]1(C)C(F)(F)F)C2=NC3=C(N2)C=C(C(F)=C3)OC[C@@H](CO)O)C4=C(C(F)=C(C=C4)F)OC(F)([2H])F
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
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-26 Related Classifications
HY-189848S Related Classifications
Powered by Bioz