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  4. URB602

URB602 是一種選擇性的單酰基甘油脂肪酶 (MGL) 抑制劑，非競爭性抑制大鼠腦 MGL，IC50 為 28±4 μM。

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URB602 Chemical Structure

URB602 Chemical Structure

CAS No. : 565460-15-3

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規(guī)格 價格 是否有貨 數(shù)量
10 mM * 1 mL in DMSO ￥330
In-stock
5 mg ￥300
In-stock
10 mg ￥500
In-stock
25 mg ￥800
In-stock
50 mg ￥1400
In-stock
100 mg ￥2500
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200 mg   詢價  
500 mg   詢價  

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Customer Review

  • 生物活性

  • 實驗參考方法

  • 純度 & 產(chǎn)品資料

  • 參考文獻(xiàn)

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]
體外研究
(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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
體內(nèi)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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
分子量

295.38

Formula

C19H21NO2
CAS 號
性狀

固體

顏色

White to off-white

運輸條件

Room temperature in continental US; may vary elsewhere.
儲存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
溶解性數(shù)據(jù)
細(xì)胞實驗： 

DMSO 中的溶解度 : 100 mg/mL (338.55 mM; 超聲助溶; 吸濕的 DMSO 對產(chǎn)品的溶解度有顯著影響，請使用新開封的 DMSO)

配制儲備液
濃度 溶劑體積 質(zhì)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
查看完整儲備液配制表

* 請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲存時，請在2年內(nèi)使用， -20°C儲存時，請在1年內(nèi)使用。

  • 摩爾計算器

  • 稀釋計算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

質(zhì)量
=
濃度
×
體積
×
分子量 *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

濃度 (start)

C1

×
體積 (start)

V1

=
濃度 (final)

C2

×
體積 (final)

V2

動物實驗：

請根據(jù)您的 實驗動物和給藥方式 選擇適當(dāng)?shù)娜芙夥桨浮?

以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：
——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用；
以下溶劑前顯示的百分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

  • 方案 一

    請依序添加每種溶劑： 10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: 2.5 mg/mL (8.46 mM); 懸濁液; 超聲助溶

    此方案可獲得 2.5 mg/mL的均勻懸濁液，懸濁液可用于口服和腹腔注射。

    以 1 mL 工作液為例，取 100 μL 25.0 mg/mL 的澄清 DMSO 儲備液加到 400 μL PEG300 中，混合均勻；再向上述體系中加入 50 μL Tween-80，混合均勻；然后再繼續(xù)加入 450 μL 生理鹽水 定容至 1 mL。

    生理鹽水的配制：將 0.9 g 氯化鈉，溶解于 ddH?O 并定容至 100 mL，可以得到澄清透明的生理鹽水溶液。
  • 方案 二

    請依序添加每種溶劑： 10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (8.46 mM); 澄清溶液

    此方案可獲得 ≥ 2.5 mg/mL（飽和度未知）的澄清溶液，此方案實驗周期在半個月以上的動物實驗酌情使用。

    以 1 mL 工作液為例，取 100 μL 25.0 mg/mL 的澄清 DMSO 儲備液加到 900 μL玉米油中，混合均勻。

動物溶解方案計算器
請輸入動物實驗的基本信息：

給藥劑量

mg/kg

動物的平均體重

g

每只動物的給藥體積

μL

動物數(shù)量

只
由于實驗過程有損耗，建議您多配一只動物的量
請輸入您的動物體內(nèi)配方組成：
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
如果您的動物是免疫缺陷鼠或者體弱鼠，建議 DMSO 中的在最后工作液體系中的占比盡量不超過 2%。
方案所需 助溶劑 包括：DMSO， ，均可在 MCE 網(wǎng)站選購。 ，Tween 80，均可在 MCE 網(wǎng)站選購。
計算結(jié)果
工作液所需濃度 : mg/mL
儲備液配制方法 : mg 藥物溶于 μL  DMSO（母液濃度為 mg/mL）。
您所需的儲備液濃度超過該產(chǎn)品的實測溶解度，以下方案僅供參考，如有需要，請與 MCE 中國技術(shù)支持聯(lián)系。
動物實驗體內(nèi)工作液的配制方法 : 取 μL DMSO 儲備液，加入 μL 。 μL ，混合均勻至澄清，再加 μL Tween 80，混合均勻至澄清，再加 μL 生理鹽水。
連續(xù)給藥周期超過半月以上，請謹(jǐn)慎選擇該方案。
請確保第一步儲備液溶解至澄清狀態(tài)，從左到右依次添加助溶劑。您可采用超聲加熱 （超聲清洗儀，建議頻次 20-40 kHz），渦旋吹打等方式輔助溶解。
純度 & 產(chǎn)品資料
參考文獻(xiàn)
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].

MCE 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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
參考文獻(xiàn)

完整儲備液配制表

* 請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲存時，請在2年內(nèi)使用， -20°C儲存時，請在1年內(nèi)使用。

可選溶劑 濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.3855 mL 16.9273 mL 33.8547 mL 84.6367 mL
5 mM 0.6771 mL 3.3855 mL 6.7709 mL 16.9273 mL
10 mM 0.3385 mL 1.6927 mL 3.3855 mL 8.4637 mL
15 mM 0.2257 mL 1.1285 mL 2.2570 mL 5.6424 mL
20 mM 0.1693 mL 0.8464 mL 1.6927 mL 4.2318 mL
25 mM 0.1354 mL 0.6771 mL 1.3542 mL 3.3855 mL
30 mM 0.1128 mL 0.5642 mL 1.1285 mL 2.8212 mL
40 mM 0.0846 mL 0.4232 mL 0.8464 mL 2.1159 mL
50 mM 0.0677 mL 0.3385 mL 0.6771 mL 1.6927 mL
60 mM 0.0564 mL 0.2821 mL 0.5642 mL 1.4106 mL
80 mM 0.0423 mL 0.2116 mL 0.4232 mL 1.0580 mL
100 mM 0.0339 mL 0.1693 mL 0.3385 mL 0.8464 mL
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產(chǎn)品名稱：
URB602
目錄號：
HY-100792
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