UC-1728

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

UC-1728 是一种有效的兔可溶性环氧化物水解酶抑制剂（对兔肝脏的IC50：2 nM）。通过皮下注射 sEH 抑制剂（UC1728，3 mg/kg）或载体对照（PEG400）对兔子进行治疗，并使用改良的 Hackett-McDonald 评分系统在前房内 LPS 注射后 6、24 和 48 小时评估葡萄膜炎。

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