URB602-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEURB602Cat. No.: HY-100792CAS No.: 565460-15-3分式: CHNO分量: 295.38作靶點(diǎn): Others作通路: Others儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 31 mg/mL (104.95 mM)* means soluble, but saturation unkn

2、own.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.3855 mL 16.9273 mL 33.8547 mL5 mM 0.6771 mL 3.3855 mL 6.7709 mL10 mM 0.3385 mL 1.6927 mL 3.3855 mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 URB602種選擇性的單酰油脂酶 (MGL) 抑制劑，競(jìng)爭(zhēng)性抑制腦 MGL，IC50 為 284 M。IC50 & Target IC50: 284 M (

3、rat brain MGL) 1體外研究Without URB602, the apparent Michaelis constant (Km) of MGL for 2-AG is 241.7 M and the maximumvelocity (Vmax) is 181451 nmol min per mg protein; with URB602, the Km is 200.4 M and the Vmax is1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE54120 nmol min per mg protein (n=4). Wh

4、en organotypic slice cultures of rat forebrain are incubated withURB602 (100 M), both baseline and Ca2+-ionophore-stimulated 2-arachidonoylglycerol (2-AG)concentrations are increased 1. URB602 is an inhibitor of monoacylglycerol lipase (MGL), a serinehydrolase involved in the biological deactivation

5、 of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG).URB602 weakly inhibits recombinant MGL (IC50=22363 M) through a rapid and noncompetitivemechanism 2.體內(nèi)研究 URB602 at doses of 20 and 40 mg/kg tends to reduce upper GI transit and slow colonic propulsion. Whentaken together as whole gut transit,

6、 URB602 dose dependently inhibits transit (P1 receptor involvement in theinhibitory action 3. URB602 decreases the AUC of pain behaviour during the early phase of the formalin testwith an ED50 of 0.060.028 g for JZL184 and 12051.3 g for URB602 in adult male Sprague-Dawley rats.Both MGL inhibitors al

7、so suppresses pain behaviour during the late phase of formalin pain, with an ED50 of0.030.011 g for JZL184 and 6623.9 g for URB602 4.PROTOCOLKinase Assay 2 Samples containing either URB602 (300 M), MGL (1.4 pM), or both URB602 and MGL are incubated at37C for 30 min in assay buffer. At various time p

8、oints, 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 (1502.1 mmi.d., 5 m) eluted is used with a linear gradient of methanol in water containing 0.25% acetic acid and 5 mMammonium acetate (from 60% to 100%

9、of methanol in 8 min) at a flow rate of 0.5 mL/min with columntemperature at 50C. Capillary voltage is set at 4 kV and fragmentor voltage is 100V. Nebulizer pressure isset at 60 psi. N2 is used as drying gas at a flow rate of 13 liters/min and a temperature of 350C. ESI is in thepositive mode and a

10、full scan spectrum is acquired from m/z 100 to 600. Extracted ion chromatograms areused 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 Mice 3Administration 34 Male C57BL/6 mice (5-6 wk; 20-26 g) or female CB1

11、-/- mice (8 wk; 18-22 g) on a C57BL/6 background areused. After an overnight fasting period (water ad libitum), a marker is administered orally to assess upper GItransit, as described in detail by others. At 30 min after intraperitoneal (ip) administration of URB602 (20 or40 mg/kg) or vehicle (10% D

12、MSO/Tween 80 in saline), an oral gavage of 200 L of an Evans blue marker(5% Evans blue, 5% gum arabic) is administered. After 15 min animals are killed by cervical dislocation andthe intestine from the region of the pyloric sphincter to the ileocecal junction is immediately removed. Thedistance trav

13、eled by the marker is measured in centimeters and expressed as a percentage of the totallength of the small intestine.Rats 4Three hundred and seven adult male Sprague-Dawley rats weighing 275-350 g, at the time of testing, areused. In a first study, the dose-response curves for JZL184 and URB602 are

14、 determined using the AUC ofPhase 1 or Phase 2 pain behaviour. In a second study, the antinociceptive effects of JZL184 (300 g) andURB602 (600 g) are evaluated following injection in the paw, ipsilateral or contralateral to formalin, toexclude the possibility that systemic leakage contributed to the

15、 pattern of results obtained. In a third study,antinociceptive effects of ED50 doses of JZL184 (0.03 g i.paw) or URB602 (66 g i.paw), in combination2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEwith 2-AG (ED50 dose of 1 g i.paw), are quantified to evaluate the presence of additive or synergic eff

16、ectsof these drugs. In a fourth study, antinociceptive effects of JZL184 (at 10 g i.paw, an analgesic dose) arestudied in the presence or absence of either AM251 or AM630 to determine whether these effects aremediated through CB1 and/or CB2 receptors. The CB1 receptor antagonist AM251 exhibits 306-f

17、oldselectivity for CB1 over CB2 receptors, whereas the CB2 receptor antagonist AM630 exhibits 70-165-foldselectivity for CB2 over CB1 receptors. The doses employed (AM251 at 80 g i.paw and AM630 at 25 gi.paw) are those which block peripheral antinociceptive effects of URB602 in Wistar rats. For the

18、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=6per group), drugs, administered either alone or in combination, are dissolved in the same total volume (50 L) and injected into the right hind paw. Preliminary experiments (n=8 per gr

19、oup; data not shown) confirmedthat formalin-induced pain behaviour did not change following intra-paw administration of either vehicle (PEG300: 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.REFERENCES1. 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 selectiv