A-967079

Names

[ Name ]:
A-967079

[Synonym ]:
A967079 /A-967079
(1E,3E)-1-(4-Fluorophenyl)-2-methyl-1-penten-3-one oxime
(1E,3E)-1-(4-fluorophenyl)-2-methylpent-1-en-3-one oxime
(1E,3E)-1-(4-FLUOROPHENYL)-2-METHYL-1-PENTEN-3-ONEOXIME
A-967079

Biological Activity

[Description]:

A-967079 is a selective TRPA1 receptor antagonist with IC50s of 67 nM and 289 nM at human and rat TRPA1 receptors, respectively, and has good penetration into the CNS.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Inflammation/Immunology

[Target]

IC50: 67 nM (human TRPA1 receptor), 289 nM (rat TRPA1 receptor)[1]

[In Vivo]

Systemic injection of A-967079 (30 μmol/kg, i.v.) decreases the responses of wide dynamic range (WDR), and nociceptive specific (NS) neurons following noxious pinch stimulation of the ipsilateral hind paw in uninjured and CFA-inflamed rats. Similar to its actions in uninjured rats, administration of A-967079 (30 μmol/kg, i.v.) to complete Freund's adjuvant (CFA)-inflamed rats significantly reduces WDR neuronal responses to noxious pinch stimulation compared to baseline firing (p=0.0013, repeated-measures ANOVA) and the vehicle group (p=0.0001, two-way ANOVA). The maximum observed effect (61.1±10.97% decrease from baseline levels) on pinch-evoked activity in inflamed rats occur 35 min after injection. In contrast to uninjured rats, injection of A-967079 to CFA-inflamed rats also significantly (p=0.0004, and p=0.0001 for the repeated-measures and two-way ANOVA's, respectively) reduces responses of WDR neurons to 10-g von Frey hair stimulation. The maximal observed decrease in von Frey-evoked activity is 67.69±18.39% from baseline levels (35 min post-injection), and is thus comparable to the effects of A-967079 on pinch-evoked activity in inflamed rats[1].

[Animal admin]

Rats[1] Male Sprague-Dawley rats (250-400 g) are used for all experiments and are housed in a temperature controlled room with a 12/12-hr day/night cycle. Food and water are available ad libitum. Spontaneous and evoked neuronal activity is then measured 5, 15, 25, and 35 min after systemic injection of A-967079 (30 μmol/kg, i.v.) or vehicle (polyethylene glycol). The intravenous injection of A-967079 or vehicle is completed over a 6-7 min period. The i.v. dose of A-967079 is selected based on extrapolated plasma levels that are effective in behavioral studies[1].

[References]

[1]. McGaraughty S, et al. TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats. Mol Pain. 2010 Mar 5;6:14.

[Related Small Molecules]

capsaicin | Capsazepine | EIPA | Diphenyleneiodonium chloride | HC-030031 | SKF-96365 | HC 067047 | AMG 9810 | GSK-1016790A | SAR7334 | PF-4840154 | RN-1734 | AMG-517 | SB-366791 | IcilinAG-3-5

Chemical & Physical Properties

[ Density]:
1.0±0.1 g/cm3

[ Boiling Point ]:
324.4±34.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₂H₁₄FNO

[ Molecular Weight ]:
207.244

[ Flash Point ]:
150.0±25.7 °C

[ Exact Mass ]:
207.105942

[ PSA ]:
32.59000

[ LogP ]:
3.73

[ Vapour Pressure ]:
0.0±0.7 mmHg at 25°C

[ Index of Refraction ]:
1.498

[ Storage condition ]:
2-8℃

[ Water Solubility ]:
Very slightly soluble (0.19 g/L) (25 ºC)

Safety Information

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2928000090

Customs

[ HS Code ]: 2928000090

[ Summary ]:
2928000090 other organic derivatives of hydrazine or of hydroxylamine VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:20.0%

Articles

TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats.

Mol. Pain 6 , 14, (2010)

There is growing evidence supporting a role for TRPA1 receptors in the neurotransmission of peripheral mechanical stimulation. In order to enhance understanding of TRPA1 contributions to mechanotransm...

Anti-inflammatory effects of N-acylethanolamines in rheumatoid arthritis synovial cells are mediated by TRPV1 and TRPA1 in a COX-2 dependent manner.

Arthritis. Res. Ther. 17 , 321, (2015)

The endocannabinoid system modulates function of immune cells and mesenchymal cells such as fibroblasts, which contribute to cartilage destruction in rheumatoid arthritis (RA). The aim of the study wa...

Related Compounds

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