UC-1728

Research use only, not for human use.

UC-1728 is an effective rabbit soluble epoxide hydrolase inhibitor (IC50: 2 nM on rabbit liver). Rabbits were treated by subcutaneous injection with the sEH inhibitor (UC1728, 3 mg/kg), or the vehicle control (PEG400) and uveitis was assessed at 6, 24 and 48 h post-intracameral LPS injection using a modified Hackett-McDonald scoring system.?

UC-1728 is an effective rabbit soluble epoxide hydrolase inhibitor (IC50: 2 nM on rabbit liver). Rabbits were treated by subcutaneous injection with the sEH inhibitor (UC1728, 3 mg/kg), or the vehicle control (PEG400) and uveitis was assessed at 6, 24 and 48 h post-intracameral LPS injection using a modified Hackett-McDonald scoring system.?Eyes treated by intra-cameral injection of PBS, or by aseptic preparation served as further controls.?Signs of inflammation in this model were mild and transient.?Treatment with UC1728 did not significantly reduce inflammation compared to animals treated with the PEG400 vehicle.?Blood levels of UC1728 were a thousand fold higher than the in vitro determined inhibitory potency (IC50) of the compound suggesting a significant degree of inhibition of sEH in the rabbit.?The lack of efficacy suggests that sEH or its substrates the EETs may not be involved in mediating inflammation in this model of uveitis.

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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. 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. 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.

t-TUCB

Others

Other Targets

epoxide hydrolase

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948304-40-3

438.4

C21H21F3N2O5

>98% (HPLC)

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FC(F)(F)OC(C=C1)=CC=C1NC(N[C@@H](CC2)CC[C@H]2OC3=CC=C(C(O)=O)C=C3)=O

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(-20℃)

With Ice Pack

≥ 2 years