AP-18

AP-18用途

AP-18 是一种选择性 TRPA1 抑制剂,AP-18 阻断 50 μM 肉桂醛对 TRPA1 的激活,在人和小鼠中的 IC50 分别为 3.1 μM 和 4.5 μM。AP-18 逆转 CFA 诱导的小鼠机械性痛觉过敏。AP-18 以浓度依赖的方式减弱了 30 μM AITC 诱导的 Yo-Pro 摄取,IC50 为 10.3 μM。

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AP-18名称

[ CAS 号 ]:
55224-94-7

[ 英文名 ]:
AP-18

[英文别名 ]:

N-Desmethylclozapine
4-(4-chlorophenyl)-3-methylbut-3-en-2-one oxime
AP-18

AP-18生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> TRP频道

研究领域 >> 神经疾病

[ 靶点 ]

TRPA1:~3 μM (IC50)

[体外研究]

浓度达50μM时,AP-18不能明显阻断TRPV1、TRPV2、TRPV3、TRPV4或TRPM8的激活。AP-18可逆地阻断小鼠TRPA1对碘乙酰胺(一种不可逆的半胱氨酸烷基化剂)的反应。AP-18还阻断冷和芥末油诱导的小鼠TRPA1活化。AP-18阻断了肉桂醛诱导的爪蟾卵母细胞的TRPA1电流[1]。

[体内研究]

AP18(1 mM；小鼠后肢注射)显著阻断肉桂醛染料诱导的伤害性事件,而不是辣椒素诱导的伤害性事件,证明了其有效性和特异性[1]。

[参考文献]

[1]. Petrus M, et al. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Mol Pain. 2007;3:40. Published 2007 Dec 17.

[2]. Chen J, et al. Pore dilation occurs in TRPA1 but not in TRPM8 channels. Mol Pain. 2009;5:3. Published 2009 Jan 21.

[3]. Taylor-Clark TE, et al. Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1. Mol Pharmacol. 2009;75(4):820-829.

AP-18物理化学性质

[ 密度 ]:
1.1±0.1 g/cm3

[ 沸点 ]:
348.4±34.0 °C at 760 mmHg

[ 分子式 ]:
C₁₁H₁₂ClNO

[ 分子量 ]:
209.672

[ 闪点 ]:
164.5±25.7 °C

[ 精确质量 ]:
209.060745

[ PSA ]:
32.59000

[ LogP ]:
3.72

[ 蒸汽压 ]:
0.0±0.8 mmHg at 25°C

[ 折射率 ]:
1.529

[ 储存条件 ]:
-20°C，密闭，干燥

AP-18安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Faceshields;Gloves

[ 危害码 (欧洲) ]:
Xn

[ 风险声明 (欧洲) ]:
22

[ 危险品运输编码 ]:
NONH for all modes of transport

AP-18文献

TRPA1 has a key role in the somatic pro-nociceptive actions of hydrogen sulfide.

PLoS ONE 7(10) , e46917, (2012)

Hydrogen sulfide (H(2)S), which is produced endogenously from L-cysteine, is an irritant with pro-nociceptive actions. We have used measurements of intracellular calcium concentration, electrophysiolo...

TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice.

PLoS ONE 4 , e7596, (2009)

Nitric oxide (NO) can induce acute pain in humans and plays an important role in pain sensitization caused by inflammation and injury in animal models. There is evidence that NO acts both in the centr...

A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor α-induced inflammatory hyperalgesia and Freund's complete adjuvant-induced monarthritis.

Arthritis Rheum. 63 , 819-29, (2011)

To investigate the involvement of transient receptor potential ankyrin 1 (TRPA1) in inflammatory hyperalgesia mediated by tumor necrosis factor α(TNFα) and joint inflammation.Mechanical hyperalgesia w...

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