| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Voltage‑gated sodium channel NaV1.8 (SCN10A).
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| ln Vitro |
Blocking Na(v)1.2 is about three times less effective with A-887826, blocking tetrodotoxin-sensitive sodium (TTX-S Na(+)) currents is around ten times less effective, and blocking Na(v)> 30 times)1.5 channels is about ten times less effective[1]. In a voltage-dependent manner (IC50=8 nM), A-887826 potently inhibits tetrodotoxin-resistant sodium (TTX-R Na(+)) currents from small-diameter rat dorsal root ganglion (DRG) neurons[1]. In rats given Freund's adjuvant-induced inflammation, A-887826 reversibly inhibits the spontaneous firing of small-diameter DRG neurons and effectively blocks evoked action potential discharges when DRG neurons maintain depolarizing potentials [1]. Without altering voltage-dependent activation, A-887826 (100 nM) shifts the midpoint of voltage-dependent inactivation of TTX-R currents by around 4 mV and does not show frequency-dependent inhibition [1].
Whole‑cell patch clamp on HEK293 cells expressing human NaV1.8: A-887826 blocks peak current with IC50 = 11 nM at holding potential -60 mV (use‑dependent). At -120 mV, IC50 = 1.2 uM (showing state dependence). Selectivity: >100-fold over NaV1.2,1.5,1.7. Inhibits tetrodotoxin‑resistant current in rat DRG neurons. |
| ln Vivo |
In a rat neuropathic pain model, A-887826 (3–30 mg/kg; oral; 1 hour before treatment) effectively improves tactile allodynia [1].
In rat spinal nerve ligation (SNL) neuropathic pain model, oral A-887826 (30 mg/kg) reduces mechanical allodynia by 65% at 2 h post‑dose (paw withdrawal threshold from 4.5 g to 13.5 g). In CFA model, ED50 = 18 mg/kg p.o. Reverses spontaneous pain as measured by conditioned place preference. |
| Enzyme Assay |
State‑dependent block assay: NaV1.8 channels in HEK293 cells subjected to two holding potentials: -120 mV (resting) or -60 mV (depolarized). A-887826 (0.1-1000 nM) applied; peak currents elicited by 50 ms depolarization to +10 mV; ratio of IC50 at -60 mV to IC50 at -120 mV (use‑dependence ratio = 0.009).
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| Cell Assay |
DRG neuron isolation: lumbar DRGs from adult rats; neurons cultured for 24 h; whole‑cell patch clamp at 22degC; current-clamp mode to record action potentials; A-887826 (100 nM) superfused; reduces number of evoked spikes by 80% and suppresses spontaneous firing in inflamed (CFA) DRGs.
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| Animal Protocol |
Animal/Disease Models: Male Spraguee Dawley rat (200-300 g) [1]
Doses: 3 mg/kg, 10 mg/kg, 30 mg/kg Route of Administration: oral; Route of Administration: oral. 1 hour before testing; Fourteen days after L5-L6 spinal nerve ligation Experimental Results: A dose-dependent attenuation of tactile allodynia was produced in this experimental pain model. Rat SNL model: L5/L6 spinal nerves ligated; after 14 days, rats with allodynia (threshold <6 g) receive A-887826 (3,10,30 mg/kg p.o.) or gabapentin (100 mg/kg p.o.); von Frey test at 0.5,1,2,4 h; efficacy expressed as % reversal of allodynia (baseline = pre‑surgery threshold, 15 g). |
| ADME/Pharmacokinetics |
Rat p.o. 30 mg/kg: Cmax ~6.2 uM at 1.5 h; t1/2 ~6 h; oral bioavailability ~44%; plasma protein binding ~96%; volume of distribution ~3.2 L/kg; low brain/plasma ratio (0.1); metabolized by CYP2C19 and CYP3A4; renally excreted (40% unchanged).
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| Toxicity/Toxicokinetics |
Rats: up to 100 mg/kg/day for 14 days p.o. no significant toxicity (no ataxia, no GI lesions). Dog 28‑day study (30 mg/kg/day) shows mild elevation of liver enzymes (ALT 2× ULN) but reversible. No hERG inhibition (IC50 >30 uM). CNS side effects minimal compared to NaV1.7 blockers.
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| References | |
| Additional Infomation |
Phase I clinical trials completed (NCT01547481) but not approved. Showed analgesic effect in acute pain models (dental pain) but development stopped likely due to insufficient efficacy or PK issues. Still a key tool for studying NaV1.8 in pain transduction. More selective than A-803467.
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| Molecular Formula |
C₂₆H₂₉CLN₄O₃
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|---|---|
| Molecular Weight |
480.99
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| Exact Mass |
480.193
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| CAS # |
1266212-81-0
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| PubChem CID |
46919335
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| Appearance |
White to off-white solid powder
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| LogP |
5.382
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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 |
9
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| Heavy Atom Count |
34
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| Complexity |
621
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JPJGFWKHSMUKFO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H29ClN4O3/c1-2-3-11-34-24-7-6-19(15-23(24)27)21-14-22(17-28-16-21)26(32)30-18-20-5-4-8-29-25(20)31-9-12-33-13-10-31/h4-8,14-17H,2-3,9-13,18H2,1H3,(H,30,32)
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| Chemical Name |
5-(4-butoxy-3-chlorophenyl)-N-[(2-morpholin-4-ylpyridin-3-yl)methyl]pyridine-3-carboxamide
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| Synonyms |
A887826; A 887826
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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 : ~250 mg/mL (~519.76 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0790 mL | 10.3952 mL | 20.7905 mL | |
| 5 mM | 0.4158 mL | 2.0790 mL | 4.1581 mL | |
| 10 mM | 0.2079 mL | 1.0395 mL | 2.0790 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.
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