URB602

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

URB602  纯度: 99.49%

URB602 是一种选择性的单酰基甘油脂肪酶 (MGL) 抑制剂,非竞争性抑制大鼠脑 MGL,IC50 为 28±4 μM。

URB602

URB602 Chemical Structure

CAS No. : 565460-15-3

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥550 In-stock
10 mg ¥500 In-stock
25 mg ¥800 In-stock
50 mg ¥1400 In-stock
100 mg ¥2500 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

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生物活性

URB602 is a selective monoacylglycerol lipase (MGL) inhibitor, which inhibits rat brain MGL with IC50 of 28±4 μM through a noncompetitive mechanism.

IC50 & Target

IC50: 28±4 μM (rat brain MGL)[1]

体外研究
(In Vitro)

Without URB602, the apparent Michaelis constant (Km) of MGL for 2-AG is 24±1.7 μM and the maximum velocity (Vmax) is 1814±51 nmol min per mg protein; with URB602, the Km is 20±0.4 μM and the Vmax is 541±20 nmol min per mg protein (n=4). When organotypic slice cultures of rat forebrain are incubated with URB602 (100 μM), both baseline and Ca2+-ionophore-stimulated 2-arachidonoylglycerol (2-AG) concentrations are increased[1]. URB602 is an inhibitor of monoacylglycerol lipase (MGL), a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). URB602 weakly inhibits recombinant MGL (IC50=223±63 μM) through a rapid and noncompetitive mechanism[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

URB602 at doses of 20 and 40 mg/kg tends to reduce upper GI transit and slow colonic propulsion. When taken together as whole gut transit, URB602 dose dependently inhibits transit (P<0.05) compared with the vehicle control group. The inhibitory action of 40 mg/kg URB602 on whole gut transit is absent in these mice, indicating CB1 receptor involvement in the inhibitory action[3]. URB602 decreases the AUC of pain behaviour during the early phase of the formalin test with an ED50 of 0.06±0.028 μg for JZL184 and 120±51.3 μg for URB602 in adult male Sprague-Dawley rats. Both MGL inhibitors also suppresses pain behaviour during the late phase of formalin pain, with an ED50 of 0.03±0.011 μg for JZL184 and 66±23.9 μg for URB602[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

分子量

295.38

Formula

C19H21NO2

CAS 号

565460-15-3

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 100 mg/mL (338.55 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 3.3855 mL 16.9273 mL 33.8547 mL
5 mM 0.6771 mL 3.3855 mL 6.7709 mL
10 mM 0.3385 mL 1.6927 mL 3.3855 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: 2.5 mg/mL (8.46 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.5 mg/mL (8.46 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (8.46 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (8.46 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Hohmann AG, et al. An endocannabinoid mechanism for stress-induced analgesia. Nature. 2005 Jun 23;435(7045):1108-12.

    [2]. King AR, et al. URB602 inhibits monoacylglycerol lipase and selectively blocks 2-arachidonoylglycerol degradation in intact brain slices. Chem Biol. 2007 Dec;14(12):1357-65.

    [3]. Duncan M, et al. Distribution and function of monoacylglycerol lipase in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2008 Dec;295(6):G1255-65.

    [4]. Guindon J, et al. Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain. Br J Pharmacol. 2011 Aug;163(7):1464-78.

Kinase Assay
[2]

Samples containing either URB602 (300 μM), MGL (1.4 pM), or both URB602 and MGL are incubated at 37°C for 30 min in assay buffer. At various time points, the reaction is stopped with an equal volume of ice-cold methanol and directly analyzed in positive ionization mode by LC/MS. A SB-CN column (150×2.1 mm i.d., 5 μm) eluted is used with a linear gradient of methanol in water containing 0.25% acetic acid and 5 mM ammonium acetate (from 60% to 100% of methanol in 8 min) at a flow rate of 0.5 mL/min with column temperature at 50°C. Capillary voltage is set at 4 kV and fragmentor voltage is 100V. Nebulizer pressure is set at 60 psi. N2 is used as drying gas at a flow rate of 13 liters/min and a temperature of 350°C. ESI is in the positive mode and a full scan spectrum is acquired from m/z 100 to 600. Extracted ion chromatograms are used to quantify URB602 ([M+H]+, m/z 296)[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[3][4]

Mice[3]
Male C57BL/6 mice (5-6 wk; 20-26 g) or female CB1-/- mice (8 wk; 18-22 g) on a C57BL/6 background are used. After an overnight fasting period (water ad libitum), a marker is administered orally to assess upper GI transit, as described in detail by others. At 30 min after intraperitoneal (ip) administration of URB602 (20 or 40 mg/kg) or vehicle (10% DMSO/Tween 80 in saline), an oral gavage of 200 μL of an Evans blue marker (5% Evans blue, 5% gum arabic) is administered. After 15 min animals are killed by cervical dislocation and the intestine from the region of the pyloric sphincter to the ileocecal junction is immediately removed. The distance traveled by the marker is measured in centimeters and expressed as a percentage of the total length of the small intestine.
Rats[4]
Three hundred and seven adult male Sprague-Dawley rats weighing 275-350 g, at the time of testing, are used. In a first study, the dose-response curves for JZL184 and URB602 are determined using the AUC of Phase 1 or Phase 2 pain behaviour. In a second study, the antinociceptive effects of JZL184 (300 μg) and URB602 (600 μg) are evaluated following injection in the paw, ipsilateral or contralateral to formalin, to exclude the possibility that systemic leakage contributed to the pattern of results obtained. In a third study, antinociceptive effects of ED50 doses of JZL184 (0.03 μg i.paw) or URB602 (66 μg i.paw), in combination with 2-AG (ED50 dose of 1 μg i.paw), are quantified to evaluate the presence of additive or synergic effects of these drugs. In a fourth study, antinociceptive effects of JZL184 (at 10 μg i.paw, an analgesic dose) are studied in the presence or absence of either AM251 or AM630 to determine whether these effects are mediated through CB1 and/or CB2 receptors. The CB1 receptor antagonist AM251 exhibits 306-fold selectivity for CB1 over CB2 receptors, whereas the CB2 receptor antagonist AM630 exhibits 70-165-fold selectivity for CB2 over CB1 receptors. The doses employed (AM251 at 80 μg i.paw and AM630 at 25 μg i.paw) are those which block peripheral antinociceptive effects of URB602 in Wistar rats. For the first study (n=4-6 per group for URB602 and n=6-8 per group for JZL184) and for all the other behavioural studies (n=6 per group), drugs, administered either alone or in combination, are dissolved in the same total volume (50 μL) and injected into the right hind paw. Preliminary experiments (n=8 per group; data not shown) confirmed that formalin-induced pain behaviour did not change following intra-paw administration of either vehicle (PEG 300: Tween 80 in a 4:1 ratio or DMSO: ethanol: cremophor: 0.9% saline in a 1:1:1:17 ratio].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Hohmann AG, et al. An endocannabinoid mechanism for stress-induced analgesia. Nature. 2005 Jun 23;435(7045):1108-12.

    [2]. King AR, et al. URB602 inhibits monoacylglycerol lipase and selectively blocks 2-arachidonoylglycerol degradation in intact brain slices. Chem Biol. 2007 Dec;14(12):1357-65.

    [3]. Duncan M, et al. Distribution and function of monoacylglycerol lipase in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2008 Dec;295(6):G1255-65.

    [4]. Guindon J, et al. Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain. Br J Pharmacol. 2011 Aug;163(7):1464-78.

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