UC-1728 (t-TUCB)

UC-1728 is a potent rabbit soluble epoxide hydrolase (sEH) inhibitor, with an IC50 of 2 nM on rabbit liver.

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

Research Areas >> Cardiovascular Disease

IC50: 2 nM (rabbit sHE)[1].

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].

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].

[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.

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