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A-803467 Sodium Channel inhibitor

Cat.No.S2785

A-803467 is a selective NaV1.8 channel blocker with IC50 of 8 nM, blocks tetrodotoxin-resistant currents, exhibits >100-fold selectivity against human NaV1.2, NaV1.3, NaV1.5, and NaV1.7.
A-803467 Sodium Channel inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 357.79

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Quality Control

Batch: S278501 DMSO]72 mg/mL]false]Ethanol]11 mg/mL]false]Water]Insoluble]false Purity: 99.45%
99.45

Solubility

In vitro
Batch:

DMSO : 72 mg/mL (201.23 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 11 mg/mL

Water : Insoluble

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In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 357.79 Formula

C19H16ClNO4

 Storage (From the date of receipt)
CAS No. 944261-79-4 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles COC1=CC(=CC(=C1)NC(=O)C2=CC=C(O2)C3=CC=C(C=C3)Cl)OC

Mechanism of Action

Features
The 1st small-molecule blocker of sodium channels showing both high potency and significant subtype-selectivity among the sodium channel family.
Targets/IC50/Ki
Na(V1.8) channel
8 nM
In vitro
A-803467 potently blocks recombinant human or rat NaV1.8 channels with IC50 of 8 nM and 45 nM, respectively, at a holding potential of -40 mV. At a resting state, this compound also potently blocks human NaV1.8 channels with IC50 of 79 nM. It blocks tetrodotoxin-resistant (TTX-R) currents in rat dorsal root ganglion neurons in a concentration-dependent manner with IC50 of 140 nM, more potently compared with both mexiletine and lamotrigine with IC50 of >30 μM. This chemical displays 300- to 1,000-fold higher selectivity for hNaV1.8 over hNaV1.2, hNaV1.3, hNaV1.5, and hNaV1.7 channels with IC50 of 7.38 μM, 2.45 μM, 7.34 μM, and 6.74 μM, respectively. It shows no significant activity against other channels and receptors expressed in peripheral sensory neurons including TRPV1, P2X2/3, CaV2.2 and KCNQ2/3 channels with IC50 >10 μM. This compound also shows no or weak activity against a broad screening panel of cell-surface receptors, ion channels, and enzymes with IC50 of >2 μM. It at 0.3 μM but not 0.1 μM significantly inhibits the generation of spontaneous and electrically evoked action potentials.
In vivo
Consistent with its effects on neuronal action potential electrogenesis in vitro, systemic administration of A-803467 (20 mg/kg, i.v.) to spinal nerve ligated rats, significantly reduces both spontaneous and von Frey hairevoked firing of spinal dorsal horn wide dynamic range neurons by 66% and 53%, respectively, compared with baseline levels. Administration of this compound also dose-dependently reduces mechanical allodynia in a variety of rat pain models including spinal nerve ligation (ED50 = 47 mg/kg, i.p.), sciatic nerve injury (ED50 = 85 mg/kg, i.p.), capsaicin-induced secondary mechanical allodynia (ED50 ≈ 100 mg/kg, i.p.), and thermal hyperalgesia after intraplantar complete Freund's adjuvant injection (ED50 = 41 mg/kg, i.p.). This chemical is inactive against formalin-induced nociception and acute thermal and postoperative pain, as well as in a chemotherapy-induced pain model (vincristine).
References

Applications

Methods Biomarkers Images PMID
Western blot HERC2 / USP33 / USP20
S7285-WB1
24855649

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