A-803467 | CAS#944261-79-4 | blocker of NaV1.8 channels

MedKoo Cat#: 522388 | Name: A-803467

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

A-803467 is a potent and selective blocker of NaV1.8 channels (IC50 values are 8, 2450, 6740, 7340 and 7380 nM for hNaV1.8, hNaV1.3, hNaV1.7, hNaV1.5 and hNaV1.2 channels respectively). A-803467 affects multiple biophysical characteristics of the canonical cardiac Nav1.5 channel and our data can be used to study potential applications of A-803467 as an antiarrhythmic drug. A-803467 attenuates spinal neuronal activity in neuropathic rats. A-803467 also attenuates neuropathic and inflammatory pain in the rat.

Chemical Structure

A-803467

CAS#944261-79-4

Theoretical Analysis

MedKoo Cat#: 522388

Name: A-803467

CAS#: 944261-79-4

Chemical Formula: C19H16ClNO4

Exact Mass: 357.0768

Molecular Weight: 357.79

Elemental Analysis: C, 63.78; H, 4.51; Cl, 9.91; N, 3.91; O, 17.89

Price and Availability

Size	Price	Availability
100mg	USD 450.00	2 Weeks
200mg	USD 750.00	2 Weeks
500mg	USD 1,250.00	2 weeks
1g	USD 2,150.00	2 Weeks
2g	USD 3,250.00	2 Weeks
5g	USD 6,750.00	2 Weeks

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Related CAS #

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Synonym

A-803467; A 803467; A803467.

IUPAC/Chemical Name

5-(4-Chlorophenyl)-N-(3,5-dimethoxyphenyl)-2-furancarboxamide

InChi Key

VHKBTPQDHDSBSP-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H16ClNO4/c1-23-15-9-14(10-16(11-15)24-2)21-19(22)18-8-7-17(25-18)12-3-5-13(20)6-4-12/h3-11H,1-2H3,(H,21,22)

SMILES Code

O=C(C1=CC=C(C2=CC=C(Cl)C=C2)O1)NC3=CC(OC)=CC(OC)=C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

A 803467 is a selective Nav1.8 sodium channel blocker with an IC50 of 8 nM.

In vitro activity:

A-803467 changed sodium current inactivation kinetics and reduced peak sodium currents in a dose-dependent manner. The current (normalized to cell size)–voltage curves in control (DMSO) and in the presence of A-803467 at various concentrations are shown in Fig. 1D. Similar to raw current traces, the higher the A-803467 concentration, the lower the peak current density. Fig. 1E plots the peak sodium current densities at different A-803467 concentrations recorded from mouse cardiomyocytes at −30 mV. Compared to the control condition, the blocking effect of A-803467 was statistically significant at 3 and 10 µM (P<0.05 for both). Reference: Eur J Pharmacol. 2015 May 5;754:52-60. https://pubmed.ncbi.nlm.nih.gov/25701724/

In vivo activity:

Systemic i.v. administration of A-803467 (10–30 mg/kg) attenuated both spontaneous and von Frey-evoked (10 g) firing of WDR neurons in SNL rats (Fig. 2). WDR responses to 10-g von Frey stimulation of the hindpaw was significantly (p < 0.05) decreased from baseline levels 5 min after injection of all doses. Spontaneous activity of WDR neurons was also significantly (p < 0.05) decreased 5 min after injection of the 20 and 30 mg/kg doses of A-803467 and remained significantly decreased for the rest of the recording period. Maximal effects were observed 35 min after injection, when 30 mg/kg of A-803467 reduced spontaneous firing by 97.7 ± 1.3% and decreased the evoked responses of WDR neurons by 94.4 ± 2.6%. At the 35-min time point, spontaneous and evoked WDR neuronal firing was also significantly (p < 0.05) attenuated by 20 mg/kg (66.2 ± 13.1% and 53.2 ± 18.4%, respectively) but not by 10 mg/kg A-803467. Reference: J Pharmacol Exp Ther. 2008 Mar;324(3):1204-11 https://jpet.aspetjournals.org/content/324/3/1204.long

	Solvent	mg/mL	mM
Solubility
	DMSO	45.7	127.73
	DMF	30.0	83.85
	Ethanol	7.5	20.91

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 357.79 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Anreddy N, Patel A, Zhang YK, Wang YJ, Shukla S, Kathawala RJ, Kumar P, Gupta P, Ambudkar SV, Wurpel JN, Chen ZS, Guo H. A-803467, a tetrodotoxin-resistant sodium channel blocker, modulates ABCG2-mediated MDR in vitro and in vivo. Oncotarget. 2015 Nov 17;6(36):39276-91. doi: 10.18632/oncotarget.5747. PMID: 26515463; PMCID: PMC4770772. 2. Han Z, Jiang Y, Xiao F, Cao K, Wang DW. The effects of A-803467 on cardiac Nav1.5 channels. Eur J Pharmacol. 2015 May 5;754:52-60. doi: 10.1016/j.ejphar.2015.02.019. Epub 2015 Feb 19. PMID: 25701724. 3. Brozmanova M, Svajdova S, Pavelkova N, Muroi Y, Undem BJ, Kollarik M. The voltage-gated sodium channel NaV1.8 blocker A-803467 inhibits cough in the guinea pig. Respir Physiol Neurobiol. 2019 Dec;270:103267. doi: 10.1016/j.resp.2019.103267. Epub 2019 Aug 6. PMID: 31398537. 4. McGaraughty S, Chu KL, Scanio MJ, Kort ME, Faltynek CR, Jarvis MF. A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic rats. J Pharmacol Exp Ther. 2008 Mar;324(3):1204-11. doi: 10.1124/jpet.107.134148. Epub 2007 Dec 18. PMID: 18089840.

In vitro protocol:

In vivo protocol:

1. Brozmanova M, Svajdova S, Pavelkova N, Muroi Y, Undem BJ, Kollarik M. The voltage-gated sodium channel NaV1.8 blocker A-803467 inhibits cough in the guinea pig. Respir Physiol Neurobiol. 2019 Dec;270:103267. doi: 10.1016/j.resp.2019.103267. Epub 2019 Aug 6. PMID: 31398537. 2. McGaraughty S, Chu KL, Scanio MJ, Kort ME, Faltynek CR, Jarvis MF. A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic rats. J Pharmacol Exp Ther. 2008 Mar;324(3):1204-11. doi: 10.1124/jpet.107.134148. Epub 2007 Dec 18. PMID: 18089840.

1: Anreddy N, Patel A, Zhang YK, Wang YJ, Shukla S, Kathawala RJ, Kumar P, Gupta P, Ambudkar SV, Wurpel JN, Chen ZS, Guo H. A-803467, a tetrodotoxin-resistant sodium channel blocker, modulates ABCG2-mediated MDR in vitro and in vivo. Oncotarget. 2015 Nov 17;6(36):39276-91. doi: 10.18632/oncotarget.5747. PMID: 26515463; PMCID: PMC4770772. 2: Huang X, Jin X, Huang G, Huang J, Wu T, Li Z, Chen J, Kong F, Pan X, Yan N. Structural basis for high-voltage activation and subtype-specific inhibition of human Nav1.8. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2208211119. doi: 10.1073/pnas.2208211119. Epub 2022 Jul 19. PMID: 35858452; PMCID: PMC9335304. 3: Han Z, Jiang Y, Xiao F, Cao K, Wang DW. The effects of A-803467 on cardiac Nav1.5 channels. Eur J Pharmacol. 2015 May 5;754:52-60. doi: 10.1016/j.ejphar.2015.02.019. Epub 2015 Feb 19. PMID: 25701724. 4: Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S, Zhang XF, Kort M, Carroll W, Marron B, Atkinson R, Thomas J, Liu D, Krambis M, Liu Y, McGaraughty S, Chu K, Roeloffs R, Zhong C, Mikusa JP, Hernandez G, Gauvin D, Wade C, Zhu C, Pai M, Scanio M, Shi L, Drizin I, Gregg R, Matulenko M, Hakeem A, Gross M, Johnson M, Marsh K, Wagoner PK, Sullivan JP, Faltynek CR, Krafte DS. A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5. doi: 10.1073/pnas.0611364104. Epub 2007 May 2. PMID: 17483457; PMCID: PMC1895982. 5: McGaraughty S, Chu KL, Scanio MJ, Kort ME, Faltynek CR, Jarvis MF. A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic rats. J Pharmacol Exp Ther. 2008 Mar;324(3):1204-11. doi: 10.1124/jpet.107.134148. Epub 2007 Dec 18. PMID: 18089840. 6: Brozmanova M, Svajdova S, Pavelkova N, Muroi Y, Undem BJ, Kollarik M. The voltage-gated sodium channel NaV1.8 blocker A-803467 inhibits cough in the guinea pig. Respir Physiol Neurobiol. 2019 Dec;270:103267. doi: 10.1016/j.resp.2019.103267. Epub 2019 Aug 6. PMID: 31398537. 7: Joshi SK, Honore P, Hernandez G, Schmidt R, Gomtsyan A, Scanio M, Kort M, Jarvis MF. Additive antinociceptive effects of the selective Nav1.8 blocker A-803467 and selective TRPV1 antagonists in rat inflammatory and neuropathic pain models. J Pain. 2009 Mar;10(3):306-15. doi: 10.1016/j.jpain.2008.09.007. Epub 2008 Dec 13. PMID: 19070548. 8: Chen X, Yu L, Shi S, Jiang H, Huang C, Desai M, Li Y, Barajas-Martinez H, Hu D. Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention. J Am Heart Assoc. 2016 Nov 2;5(11):e004050. doi: 10.1161/JAHA.116.004050. PMID: 27806967; PMCID: PMC5210368. 9: Casini S, Marchal GA, Kawasaki M, Nariswari FA, Portero V, van den Berg NWE, Guan K, Driessen AHG, Veldkamp MW, Mengarelli I, de Groot JR, Verkerk AO, Remme CA. Absence of Functional Nav1.8 Channels in Non-diseased Atrial and Ventricular Cardiomyocytes. Cardiovasc Drugs Ther. 2019 Dec;33(6):649-660. doi: 10.1007/s10557-019-06925-6. PMID: 31916131; PMCID: PMC6994555. 10: Qi B, Dai S, Song Y, Shen D, Li F, Wei L, Zhang C, Nie Z, Lin J, Cai L, Ge J. Blockade of NaV1.8 Increases the Susceptibility to Ventricular Arrhythmias During Acute Myocardial Infarction. Front Cardiovasc Med. 2021 Aug 2;8:708279. doi: 10.3389/fcvm.2021.708279. PMID: 34409080; PMCID: PMC8365037. 11: Yu L, Wang M, Hu D, Huang B, Zhou L, Zhou X, Wang Z, Wang S, Jiang H. Blocking the Nav1.8 channel in the left stellate ganglion suppresses ventricular arrhythmia induced by acute ischemia in a canine model. Sci Rep. 2017 Apr 3;7(1):534. doi: 10.1038/s41598-017-00642-6. PMID: 28373696; PMCID: PMC5428783. 12: Laux-Biehlmann A, Boyken J, Dahllöf H, Schmidt N, Zollner TM, Nagel J. Dynamic weight bearing as a non-reflexive method for the measurement of abdominal pain in mice. Eur J Pain. 2016 May;20(5):742-52. doi: 10.1002/ejp.800. Epub 2015 Dec 18. PMID: 26684879. 13: Chauhan DS, Swain DK, Shah N, Yadav HP, Nakade UP, Singh VK, Nigam R, Yadav S, Garg SK. Functional and molecular characterization of voltage gated sodium channel Nav 1.8 in bull spermatozoa. Theriogenology. 2017 Mar 1;90:210-218. doi: 10.1016/j.theriogenology.2016.12.010. Epub 2016 Dec 10. PMID: 28166971. 14: Browne LE, Clare JJ, Wray D. Functional and pharmacological properties of human and rat NaV1.8 channels. Neuropharmacology. 2009 Apr;56(5):905-14. doi: 10.1016/j.neuropharm.2009.01.018. Epub 2009 Jan 31. PMID: 19371587. 15: Jo S, Zhang HB, Bean BP. Use-Dependent Relief of Inhibition of Nav1.8 Channels by A-887826. Mol Pharmacol. 2023 Apr;103(4):221-229. doi: 10.1124/molpharm.122.000593. Epub 2023 Jan 12. PMID: 36635052; PMCID: PMC10029820. 16: Moon JY, Song S, Yoon SY, Roh DH, Kang SY, Park JH, Beitz AJ, Lee JH. The differential effect of intrathecal Nav1.8 blockers on the induction and maintenance of capsaicin- and peripheral ischemia-induced mechanical allodynia and thermal hyperalgesia. Anesth Analg. 2012 Jan;114(1):215-23. doi: 10.1213/ANE.0b013e318238002e. Epub 2011 Nov 29. PMID: 22127815. 17: Schuelert N, McDougall JJ. Involvement of Nav 1.8 sodium ion channels in the transduction of mechanical pain in a rodent model of osteoarthritis. Arthritis Res Ther. 2012 Jan 7;14(1):R5. doi: 10.1186/ar3553. PMID: 22225591; PMCID: PMC3392791. 18: Rahman W, Dickenson AH. Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: An in vivo electrophysiological study in the rat. Neuroscience. 2015 Jun 4;295:103-16. doi: 10.1016/j.neuroscience.2015.03.042. Epub 2015 Mar 25. PMID: 25818052; PMCID: PMC4414363. 19: Wang X, Zhou C, Liang P, Yang J, Li F, Liao D, Huang H, Liu J. Characterization of Specific Roles of Sodium Channel Subtypes in Regional Anesthesia. Reg Anesth Pain Med. 2015 Sep-Oct;40(5):599-604. doi: 10.1097/AAP.0000000000000294. PMID: 26236999. 20: Shields SD, Butt RP, Dib-Hajj SD, Waxman SG. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis. PLoS One. 2015 Mar 6;10(3):e0119067. doi: 10.1371/journal.pone.0119067. PMID: 25747279; PMCID: PMC4352054.