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AM-0902
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
AM-0902图片
CAS NO:1883711-97-4
包装与价格:
包装价格(元)
5 mg电议
10 mg电议
50 mg电议
100 mg电议

产品介绍
AM-0902 是有效的瞬时受体电位 A1 选择性拮抗剂,作用于rTRPA1和hTRPA1的IC50分别为 71 和 131 nM。

产品描述

AM-0902 is a potent and specific TRPA1 antagonist (IC50s: 71/131 nM for rTRPA1 and hTRPA1).

体外活性

AM-0902 is highly permeable (average Papp=44.5 μcm/s in MDCK cells), an unlikely substrate for P-gp (efflux ratio=1.3 in P-gp overexpressing MDCK cells), and demonstrates good solubility (PBS pH 7.4: 226 μM, SIF: 248 μM). AM-0902 shows good selectivity over other TRP channels, as no activity is observed against human TRPV1 or TRPV4, or rat TRPV1, TRPV3, or TRPM8, at concentrations up to 10 μM. AM-0902 inhibits 45Ca2+ flux upon activation of rat TRPA1 with methylglyoxal (IC50: 0.019 μM).

体内活性

AM-0902 has moderate terminal elimination half-life (t1/2=0.6 h and 2.8 h for rat (0.5 mg/kg, iv), rat (30 mg/kg, oral)). A dose-dependent reduction of allyl isothiocyanate (AITC)-induced flinching is observed for AM-0902, with a significant reduction in flinching, observed postdosing of 10 and 30 mg/kg. The unbound plasma concentrations (Cu) at 1 h for the 1, 3, 10, and 30 mg/kg doses are 0.051±0.024, 0.19±0.11, 0.58±0.35, and 2.2±0.40 μM, covering the in vitro rat TRPA1 45Ca2+ IC50 at 0.72, 2.7, 8.2, and 30.3 fold, respectively. A good exposure-response relationship is observed in this target coverage model. An unbound in vivo IC50 of 0.35 μM, which is in good agreement with the in vitro rat TRPA1 45Ca2+ IC50, and unbound in vivo IC90 of 1.7 μM are determined. It is noteworthy that at a dose of 30 mg/kg, AM-0902 engages TRPA1 at concentrations that exceed the in vivo IC90, making it a useful tool for the exploration of in vivo models of acute pain.

细胞实验

On the day of assay, culture media is removed and MDCK cells are incubated for 10 min at room temperature (RT) with 50 μL of AM-0902 in AM-0902 dilution buffer [HBSS containing 1 mM HEPES+0.1 mg/mL BSA] at final concentrations (2.0 nM to 40 μM, 1:3 ratio), followed by another 3 min incubation at RT. The reaction mixture is aspirated, and cells are washed three times with PBS containing 0.1 mg/mL BSA. Radioactivity is measured using a TopCount microplate scintillation counter. The activation of TRPA1 is measured by the cellular uptake of radioactive calcium.

动物实验

Rats are dosed orally with either vehicle (2% HPMC/1% Tween-80) or AM-0902 at 1, 3, 10, or 30 mg/kg. After 1 h, one left ventral hind paw is injected with the TRPA1 agonist AITC (0.1%). AM-0902 is also given by an intravenous (IV) injection to rats (0.5 mg/kg).

Cas No.

1883711-97-4

分子式

C17H15ClN6O2

分子量

370.8

储存和溶解度

DMSO:145 mg/mL (391.05 mM),Need ultrasonic and warming
Powder: -20°C for 3 years
In solvent: -80°C for 2 years