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Chemical Structure| 944261-79-4 Chemical Structure| 944261-79-4

Structure of A-803467
CAS No.: 944261-79-4

Chemical Structure| 944261-79-4

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A 803467 selectively block Nav1.8 sodium channel with IC50 of 8 nM.

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Product Details of A-803467

CAS No. :944261-79-4
Formula : C19H16ClNO4
M.W : 357.79
SMILES Code : O=C(C1=CC=C(C2=CC=C(Cl)C=C2)O1)NC3=CC(OC)=CC(OC)=C3
MDL No. :MFCD10574689
InChI Key :VHKBTPQDHDSBSP-UHFFFAOYSA-N
Pubchem ID :16038374

Safety of A-803467

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Sodium Channel

    Na(V1.8) channel, IC50:8 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
HEK cells 8 nM A-803467 inhibited inward currents in HEK cells Arthritis Res Ther. 2012 Jan 7;14(1):R5.
ND7/23 cells 30 nM Evaluate the selective inhibition of Nav1.8 current by A-803467 Circ Res. 2012 Jul 20;111(3):322-32.
HEK-293 cells 8 nM Block human Nav1.8 channels Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5.
GH3 cells 3 µM Suppressed the peak density of voltage-gated Na+ current (INa) Int J Mol Sci. 2020 Mar 31;21(7):2416.
Human hypertrophic cardiomyocytes 30 nM 10 min Significantly reduced the persistent Na+ current (INaL), shortened action potential duration, and decreased sarcoplasmic reticulum Ca2+ leak ESC Heart Fail. 2019 Feb;6(1):154-163.
Human atrial cardiomyocytes 30 nM 15 minutes To investigate the effect of NaV1.8 inhibition on late sodium current, results showed A-803467 significantly reduced late sodium current. Basic Res Cardiol. 2020 Feb 20;115(2):20.
Small-sized DRG neurons 5 µM Used to block Nav1.8 currents and confirm the modulation effect of BmK I on Nav1.8 Protein Cell. 2015 Jun;6(6):443-52.
Rat dorsal root ganglion neurons 140 nM Block TTX-R currents and inhibit action potential generation Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5.
ND-7/23 cells 0.73±0.08 µM (IC50) Determination of the half-maximal inhibitory concentration (IC50) of A-803467 on Na v1.8 Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2208211119.
TSA201 cells 100 nM To investigate the electrophysiological effects of A-803467 on SCN10A-SCN5A-SCN3B co-transfected TSA201 cells. Results showed that A-803467 significantly reduced INa,P and INa,L and altered channel kinetics. J Am Heart Assoc. 2016 Nov 2;5(11):e004050.
Mouse dorsal root ganglion neurons 500 nM A-803467 blocked repetitive action potential firing in DRG neurons of both HDC−/− and wild-type mice. CNS Neurosci Ther. 2013 Sep;19(9):649-58.
Mouse dorsal root ganglion neurons 300 nM A-803467 selectively blocked Nav1.8 channels, reduced the excitability of DRG neurons in HDC−/− mice, and blocked repetitive action potential firing. CNS Neurosci Ther. 2013 Sep;19(9):649-58.
Ventricular myocytes 100 nM To evaluate the effect of Nav1.8 inhibitor A-803467 on INa,Late, results showed no significant effect of A-803467 on INa,Late Int J Mol Sci. 2022 May 20;23(10):5735.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Dogs Acute atrial fibrillation model Injection into ganglionated plexi 1 μmol/0.5 mL per GP Single injection followed by 6-hour rapid atrial pacing To evaluate the effect of A-803467 on an acute atrial fibrillation model. Results showed that A-803467 significantly reduced the incidence of AF, shortened AF duration, and prolonged AF cycle length. J Am Heart Assoc. 2016 Nov 2;5(11):e004050.
Canine Acute ischemia-induced ventricular arrhythmia model Left stellate ganglion injection 10 mM, 15 mM, 20 mM Single injection Blocking the Nav1.8 channel could significantly attenuate ischemia-induced VA, primarily by suppressing LSG activity Sci Rep. 2017 Apr 3;7(1):534
Sprague-Dawley rats Sciatic nerve transection-repair model Infusion around the injured site 10 μM For 3 days A-803467 significantly attenuated Nav1.8 upregulation after sciatic nerve transection and promoted axon regeneration. Anesthesiology. 2023 Dec 1;139(6):782-800
Mice Wild-type mice Intraperitoneal injection 25 mg/kg Single dose, recorded for 45 minutes To validate the role of NaV1.8 in the cardiac response to atropine. Results showed that the heart rate response to atropine was significantly lower in wild-type mice after A-803467 treatment. Front Pharmacol. 2020 Jul 31;11:1163
Rats Neuropathic pain model (L5/L6 spinal nerve injury) Intraperitoneal injection 47 mg/kg Single dose Reduce mechanical allodynia Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5.
Wistar rats Osteoarthritis model Intra-arterial injection 500 μg Single injection A-803467 significantly reduced the firing rate of joint afferents during noxious rotation of the joint but had no effect during non-noxious rotation. In the pain studies, peripheral injection of A-803467 into OA knees attenuated hindlimb incapacitance and secondary allodynia. Arthritis Res Ther. 2012 Jan 7;14(1):R5.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.79mL

0.56mL

0.28mL

13.97mL

2.79mL

1.40mL

27.95mL

5.59mL

2.79mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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