UC-1728 (t-TUCB)
(Synonyms: t-TUCB) 目录号 : GC33883
UC-1728 (t-TUCB) 是一种有效的兔可溶性环氧化物水解酶 (sEH) 抑制剂，对兔肝脏的 IC50 为 2 nM。
Cas No.:948304-40-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[1]Eighteen male SPF New Zealand White Rabbits (2.6-3.2 Kg) are randomly assigned to 3 groups of 6 rabbits each. Rabbits in group 1 have 20 μL sterile PBS intracamerally injected in the right eye (negative control) and all other rabbits receive 100 ng LPS in 20 μL of PBS. Groups 2 and 3 are treated with anti-inflammatory drug or vehicle once daily on the following schedule: 24 h prior to intra-cameral LPS or PBS injection, the day of injection and 24 h post-injection. Group 2 receive UC-1728 (3 mg/kg, SC) and Group 3 receive PEG400 vehicle only (0.9 mL, subcutaneously, (SC)). To limit post-procedural discomfort, systemic buprenorphine (0.03 mg/kg SC) is administered immediately prior to returning rabbits to their cages upon recovery from anesthesia, then every 6-12 h for the first 24 h and as needed for the duration of the study[1]. |
References: [1]. McLellan GJ, et al. Effect of a Soluble Epoxide Hydrolase Inhibitor, UC1728, on LPS-Induced Uveitis in the Rabbit. J Ocul Biol. 2016 Jan;4(1). | |
UC-1728 is a potent rabbit soluble epoxide hydrolase (sEH) inhibitor, with an IC50 of 2 nM on rabbit liver.
Miotic, fixed pupils are observed in the treated eyes of both groups receiving LPS injections but the difference in pupillary light reflex scores is only significantly increased in the UC-1728/LPS treated group relative to the PBS group at 6 h post-injection[1]. Pretreatment with UC-1728 (t-TUCB) at 10 and 30 mg/kg, p.o., significantly prevents ISO induced increase in heart weight and elevation of CK-MB and LDH levels (p<0.05), indicating its cardioprotective effect against ISO induced cardiac injury. At 3 mg/kg, p.o. UC-1728 only shows significant protection against heart weight changes. Pretreatment with UC-1728 at 3, 10 and 30 mg/kg, p.o., significantly reduces the ISO induced infarct size (p<0.05) when compared to control. The calculated percentage reductions for these doses are found to by 15.90, 46.60 and 40.44%, respectively[2]. Inhibition of sEH with UC-1728 is associated with a significant improvement in pain scores in one horse with laminitis whose pain is refractory to the standard of care therapy. No adverse effects are noticed[3].
[1]. McLellan GJ, et al. Effect of a Soluble Epoxide Hydrolase Inhibitor, UC1728, on LPS-Induced Uveitis in the Rabbit. J Ocul Biol. 2016 Jan;4(1). [2]. Shrestha A, et al. Soluble epoxide hydrolase inhibitor, t-TUCB, protects against myocardial ischaemic injury in rats. J Pharm Pharmacol. 2014 Sep;66(9):1251-8. [3]. Guedes AG, et al. Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet Anaesth Analg. 2013 Jul;40(4):440-8.
| Cas No. | 948304-40-3 | SDF | |
| 别名 | t-TUCB | ||
| Canonical SMILES | O=C(O)C1=CC=C(O[C@H]2CC[C@H](NC(NC3=CC=C(OC(F)(F)F)C=C3)=O)CC2)C=C1 | ||
| 分子式 | C21H21F3N2O5 | 分子量 | 438.4 |
| 溶解度 | Soluble in DMSO | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.281 mL | 11.4051 mL | 22.8102 mL |
| 5 mM | 0.4562 mL | 2.281 mL | 4.562 mL |
| 10 mM | 0.2281 mL | 1.1405 mL | 2.281 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Soluble epoxide hydrolase inhibitor, t-TUCB, protects against myocardial ischaemic injury in rats
J Pharm Pharmacol 2014 Sep;66(9):1251-8.PMID:24697323DOI:10.1111/jphp.12251.
Objectives: To determine the protective role of a soluble epoxide hydrolase(sEH) inhibitor, trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB), in isoproterenol (ISO)-induced myocardial ischaemic injury in vivo. Methods: Cardioprotective activity of t-TUCB was studied against ISO-induced myocardial ischaemic injury in male Wistar rats. Cardioprotection was assessed by measuring elecrocardiographic (EKG), serum lactate dehydrogenase (LDH) and creatine kinase (CK-MB) levels, cardiac calcium and antioxidant levels, and also by measuring infarct size in the cardiac tissue. Key findings: Pretreatment with t-TUCB at 3, 10 and 30 mg/kg orally for a period of 14 days significantly prevented the changes in EKG parameters (QTc interval prolongation, ST height depression, pathological Q waves formation and T-wave inversion), serum cardiac biomarkers (CK-MB and LDH), relative heart weight, myocardial calcium levels, infarct size and the oxidative status in the cardiac tissue (lipid peroxidation, catalase and superoxide dismutase levels) when compared with the untreated control animals (P < 0.05). Conclusion: The sEH inhibitor t-TUCB significantly prevents ISO-induced myocardial ischaemic injury in rats. This study provides a preliminary confirmation of the efficacy of t-TUCB by oral administration in rats.
Anti-nociceptive efficacy of the soluble epoxide hydrolase inhibitor t-TUCB in horses with mechanically induced lameness
Res Vet Sci 2022 Dec 20;152:504-509.PMID:36174370DOI:10.1016/j.rvsc.2022.09.017.
Introduction: Soluble epoxide hydrolase (sEH) inhibitors are novel anti-inflammatory and analgesic agents that could improve pain management in horses. The objective of the present study was to evaluate the anti-nociceptive effect of a single-dose intravenous administration of the sEH inhibitor trans-4-{4-[3-(4-trifluro-methoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB) using an adjustable heart bar shoe (a-HBS) model of lameness. We hypothesized that t-TUCB would improve objective and subjective lameness measures compared to the control. Materials and methods: Reversible lameness was induced in 8 horses for 24 h using an a-HBS in a randomized, crossover design. A vehicle-control placebo (DMSO) or t-TUCB (1 mg/kg) was intravenously administered at time 0 following a baseline induced lameness evaluation. Blood was collected and lameness was objectively measured with an inertial sensor system at 0-, 1-, 3-, 6-, 12-, and 24-h time points. Front-facing videos were obtained at each time point for subjective evaluation by three blinded evaluators using a visual analog scale (VAS). Results: Treatment with t-TUCB significantly decreased (i.e. improved) lameness compared to placebo at 1-h and compared to baseline at 1-, 3-, and 6-h following administration. Lameness significantly increased (i.e. worsened) from baseline in placebo-treated horses 12 h after administration. All horses returned to baseline soundness within 24 h of reversing lameness. Conclusion: Treatment with single-dose IV administration of t-TUCB improved lameness induced by the a-HSB, suggesting that t-TUCB has anti-nociceptive effects in horses. Clinical relevance: The soluble epoxide hydrolase inhibitor, t-TUCB, is a promising novel analgesic for horses.
Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice
Int J Mol Sci 2021 Jul 31;22(15):8267.PMID:34361032DOI:10.3390/ijms22158267.
17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.
Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis
J Vet Pharmacol Ther 2018 Apr;41(2):230-238.PMID:29067696DOI:10.1111/jvp.12463.
This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 μg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independently assigned pain scores (at rest, walk and trot) and lameness scores before and up to 48 hr after t-TUCB/LPS. Responses to touching the joint skin to assess tactile allodynia, plasma, and synovial fluid (SF) t-TUCB concentrations were determined before and up to 48 hr after t-TUCB/LPS. Blood and SF were collected for clinical laboratory evaluations before and up to 48 hr after t-TUCB/LPS. Areas under the curves of pain and lameness scores were calculated and compared between control and treatments. Data were analyzed using repeated measures ANOVA with Dunnett or Bonferroni post-test. p < .05 was considered significant. Data are mean ± SEM. Compared to control, pain, lameness, and tactile allodynia were significantly lower with 1 mg/kg t-TUCB, but not the other doses. For 0.1, 0.3, and 1 mg/kg t-TUCB treatments, plasma terminal half-lives were 13 ± 3, 13 ± 0.5, and 24 ± 5 hr, and clearances were 68 ± 15, 48 ± 5, and 14 ± 1 ml hr-1 kg-1 . The 1 mg/kg t-TUCB reached the SF at high concentrations. There were no important anti-inflammatory effects. In conclusion, sEH inhibition with t-TUCB may provide analgesia in horses with inflammatory joint pain.
Effect Of Dual sEH/COX-2 Inhibition on Allergen-Induced Airway Inflammation
Front Pharmacol 2019 Sep 27;10:1118.PMID:31611798DOI:10.3389/fphar.2019.01118.
Arachidonic acid metabolites resulting from the cyclooxygenase (COX), lipoxygenase, and cytochrome P450 oxidase enzymatic pathways play pro- and anti-inflammatory roles in allergic airway inflammation (AAI) and asthma. Expression of COX-2 and soluble epoxide hydrolase (sEH) are elevated in allergic airways and their enzymatic products (e.g., prostaglandins and diols of epoxyeicosatrienoic acids, respectively) have been shown to participate in the pathogenesis of AAI. Here, we evaluated the outcome of inhibiting the COX-2 and sEH enzymatic pathways with a novel dual inhibitor, PTUPB, in A. alternata-induced AAI. Allergen-challenged mice were administered with 10 or 30 mg/kg of PTUPB, celecoxib (selective COX-2 inhibitor), t-TUCB (selective sEH inhibitor) or vehicle daily by gavage and evaluated for various features of AAI. PTUPB and t-TUCB at 30 mg/kg, but not celecoxib, inhibited eosinophilic infiltration and significantly increased levels of anti-inflammatory EETs in the lung tissue of allergen-challenged mice. t-TUCB significantly inhibited allergen-induced IL-4 and IL-13, while a less pronounced reduction was noted with PTUPB and celecoxib. Additionally, t-TUCB markedly inhibited eotaxin-2, an eosinophil-specific chemokine, which was only marginally reduced by PTUPB and remained elevated in celecoxib-treated mice. PTUPB or t-TUCB administration reversed allergen-induced reduction in levels of various lipid mediators in the lungs, with only a minimal effect noted with celecoxib. Despite the anti-inflammatory effects, PTUPB or t-TUCB did not reduce allergen-induced airway hyperresponsiveness (AHR). However, development of structural changes in the allergic airways, such as mucus hypersecretion and smooth muscle hypertrophy, was significantly inhibited by both inhibitors. Celecoxib, on the other hand, inhibited only airway smooth muscle hypertrophy, but not mucus hypersecretion. In conclusion, dual inhibition of COX-2 and sEH offers no additional advantage relative to sEH inhibition alone in attenuating various features associated with A. alternata-induced AAI, while COX-2 inhibition exerts only moderate or no effect on several of these features. Dual sEH/COX-2 inhibition may be useful in treating conditions where eosinophilic inflammation co-exists with pain-associated inflammation.