URB937是口服有效的、外周限制性的脂肪酸酰胺水解酶（FAAH）特异性抑制剂，IC50为26.8nM。
Cas No.:1357160-72-5
Sample solution is provided at 25 µL, 10mM.
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URB937 is an orally active, peripherally restricted, selective inhibitor of fatty acid amide hydrolase (FAAH) with an IC50 of 26.8nM[1]. FAAH is a membrane-bound serine hydrolase that degrades endocannabinoids such as anandamide and terminate their signal transduction[2]. URB937 regulates the endogenous cannabinoid system by selectively inhibiting peripheral FAAH activity, exerting analgesic and anti-inflammatory effects without affecting central FAAH levels[3]. URB937 is usually used in the study of neurological diseases and inflammation/immunology[4].
In vitro, URB937(0-50µM; 72h) reduced 4T1 breast cancer cells viability but did not affect non-tumor HEK293 cells viability with an EC50 of 16.7μM[5].
In vivo, URB937 (1mg/kg; i.v.) reversed the prostaglandin E2-induced bladder overactivity, increased bladder compliance, and abolished the facilitated C-fiber afferent activity in female Sprague-Dawley rats[6]. URB937 (1mg/kg; i.p.; every other day for 25 days) prevented the development of mechanical allodynia and attenuated the upregulation of pain neuropeptide CGRP and pro-inflammatory cytokines in the medulla, cervical spinal cord, and trigeminal ganglion in a rat model of trigeminal neuralgia[7].
References:
[1] Clapper JR, Moreno-Sanz G, Russo R, et al. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat Neurosci. 2010;13(10):1265-1270.
[2] Petrosino S, Di Marzo V. FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Curr Opin Investig Drugs. 2010;11(1):51-62.
[3] O'Hearn S, Diaz P, Wan BA, et al. Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies. Ann Palliat Med. 2017;6(Suppl 2):S209-S214.
[4] Greco R, Demartini C, Zanaboni A, et al. Characterization of the peripheral FAAH inhibitor, URB937, in animal models of acute and chronic migraine. Neurobiol Dis. 2021;147:105157.
[5] Slivicki RA, Xu Z, Mali SS, Hohmann AG. Brain permeant and impermeant inhibitors of fatty-acid amide hydrolase suppress the development and maintenance of paclitaxel-induced neuropathic pain without producing tolerance or physical dependence in vivo and synergize with paclitaxel to reduce tumor cell line viability in vitro. Pharmacol Res. 2019;142:267-282.
[6] Aizawa N, Gandaglia G, Hedlund P, et al. URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E2 -induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats. BJU Int. 2016;117(5):821-828.
[7] Demartini C, Greco R, Zanaboni AM, Francavilla M, Facchetti S, Tassorelli C. URB937 Prevents the Development of Mechanical Allodynia in Male Rats with Trigeminal Neuralgia. Pharmaceuticals (Basel). 2023;16(11):1626.
URB937是口服有效的、外周限制性的脂肪酸酰胺水解酶（FAAH）特异性抑制剂，IC50为26.8nM[1]。FAAH是一种膜结合丝氨酸水解酶，可降解内源性大麻素，如anandamide，并终止其信号传导[2]。URB937通过选择性抑制外周FAAH活性调节内源性大麻素系统，发挥镇痛和抗炎作用，且不影响中枢FAAH水平[3]。URB937通常用于神经系统疾病和炎症/免疫学研究[4]。
体外实验中，URB937（0-50µM；72小时）降低了4T1乳腺癌细胞的活性，但对非肿瘤HEK293细胞的活性没有影响，其EC50为16.7µM[5]。
体内实验中，URB937（1mg/kg；静脉注射）逆转了前列腺素E2诱导的大鼠膀胱过度活动，增加了膀胱顺应性，并消除了C纤维传入活动的增强[6]。URB937（1mg/kg；腹腔注射；两天一次，共25天）预防了三叉神经痛大鼠模型中机械性痛觉过敏的发展，并减弱了延髓、颈脊髓和三叉神经节中疼痛神经肽CGRP和促炎细胞因子的上调[7]。
| Cell experiment [1]: | |
Cell lines | 4T1 breast cancer cells and HEK293 cells |
Preparation Method | 4T1 mouse breast cancer cells were maintained in RPMI-1640 supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin. HEK293 cells were maintained in DMEM supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin. All the cells were kept in a 37°C incubator equipped with 5% CO2. Cells grown on 96 well plates seeded at a density of 3000 cells/well were treated with or without URB937 (0-50μM) and incubated for 72h. Cell viability was measured through the MTT assay. |
Reaction Conditions | 0-50µM; 72h |
Applications | URB937 reduced 4T1 breast cancer cells viability but did not affect non-tumor HEK293 cells viability with an EC50 of 16.7μM. |
| Animal experiment [2]: | |
Animal models | male Sprague-Dawley rats |
Preparation Method | A total of 42 adult male Sprague-Dawley rats (weight 200-250g at arrival) were used. Animals were housed in plastic boxes in groups of two with water and food available ad libitum and kept on a 12:12h light–dark cycle. Animals were habituated to the housing conditions for 1 week before the experimental testing, then subjected to chronic constriction injury surgery of the infraorbital nerve (IoN-CCI). To evaluate the effect of URB937 in preventing the development of trigeminal mechanical allodynia, the IoN-CCI animals were subjected to sub-chronic treatment with URB937 or vehicle. Specifically, the rats were treated with URB937 (1mg/kg; i.p.) or vehicle on day +1 after surgery and then every other day until day +25. URB937 was dissolved freshly on treatment days in 10% polyethylene glycol 200, 10% Tween 80, and saline. The animals were tested with Mechanical Stimulation Test (MST) the day before surgery (for baseline measurement) and on days +4, +12, +18, and +26 after surgery. On day +26, at the end of MST, the rats were sacrificed, and samples were collected for RT-PCR analysis. |
Dosage form | 1mg/kg; i.p.; every other day for 25 days |
Applications | URB937 prevented the development of mechanical allodynia and attenuated the upregulation of pain neuropeptide CGRP and pro-inflammatory cytokines in the medulla, cervical spinal cord, and trigeminal ganglion in a rat model of trigeminal neuralgia. |
References: | |
| Cas No. | 1357160-72-5 | SDF | |
| 化学名 | N-cyclohexyl-carbamic acid, 3'-(aminocarbonyl)-6-hydroxy[1,1'-biphenyl]-3-yl ester | ||
| Canonical SMILES | NC(C1=CC(C2=C(O)C=CC(OC(NC3CCCCC3)=O)=C2)=CC=C1)=O | ||
| 分子式 | C20H22N2O4 | 分子量 | 354.4 |
| 溶解度 | 10mg/mL in ethanol, or 15mg/mL in DMSO, or 10mg/mL in DMF | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8217 mL | 14.1084 mL | 28.2167 mL |
| 5 mM | 564.3 μL | 2.8217 mL | 5.6433 mL |
| 10 mM | 282.2 μL | 1.4108 mL | 2.8217 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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