Diclofenac acyl glucuronide  (Synonyms: D-1-O-G)

Diclofenac acyl glucuronide (D-1-O-G) is an orally active glucuronide metabolite of Diclofenac (HY-15036). Diclofenac acyl glucuronide exhibits SOD inhibitory activity, COX-1 inhibitory activity (IC₅₀ = 0.620 μM), and COX-2 inhibitory activity (IC₅₀ = 2.91 μM). Diclofenac acyl glucuronide induces reactive oxygen species (ROS) production and acts as a substrate of OATP2B1. Diclofenac acyl glucuronide induces small intestinal ulcers. Diclofenac acyl glucuronide can be used in research related to intestinal diseases and small intestinal ulcers^[1][2].

Diclofenac acyl glucuronide (1-300 μM; 0.1-2 min) serves as a substrate of OATP2B1 in HEK-OATP2B1 cells, with higher uptake activity at pH 6.0; its V_max is 27.8 pmol/min/mg and K_m is 15.2 μM under pH 6.0 conditions, while its V_max is 17.6 pmol/min/mg and K_m is 14.3 μM under pH 7.4 conditions^[1].
Diclofenac acyl glucuronide (100-1000 μM; 3-12 h) exhibits higher cytotoxicity against HEK-OATP2B1 cells than diclofenac (HY-15036)^[1].
Diclofenac acyl glucuronide (100-1000 μM; 1-3 h) induces time-dependent reactive oxygen species production in HEK-OATP2B1 cells, increasing reactive oxygen species levels by 5.5-fold after 3 h of treatment at 1000 μM and by 1.8-fold after 3 h of treatment at 500 μM^[1].
Diclofenac acyl glucuronide (50-1000 μM; 30 min) dose-dependently inhibits the activity of copper/zinc superoxide dismutase. After incubation at room temperature for 30 minutes, the inhibition rate reaches 27% at 250 μM and 100% at 1000 μM^[1].
Diclofenac acyl glucuronide (2 min) inhibits purified COX-1 and COX-2 enzymes. After incubation at 37℃ for 2 minutes, its IC₅₀ against COX-1 is 0.620 μM, and that against COX-2 is 2.91 μM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Treatment with Diclofenac acyl glucuronide causes more severe intestinal damage in rats than an equimolar dose of Diclofenac^[1].
Diclofenac acyl glucuronide (bile containing Diclofenac acyl glucuronide; molar amount equivalent to 4 mg/kg diclofenac; p.o.; single dose) significantly exacerbates small intestinal ulcers in Wistar rats and TR2 rats compared to equimolar free diclofenac, with the total ulcer length significantly increased in both strains^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

472.27

C₂₀H₁₉Cl₂NO₈

64118-81-6

Solid

White to off-white

O[C@H]1[C@H](OC(CC2=CC=CC=C2NC3=C(Cl)C=CC=C3Cl)=O)O[C@H](C(O)=O)[C@@H](O)[C@@H]1O

Room temperature in continental US; may vary elsewhere.

• [1]. Scialis RJ, et al. Elucidation of the Mechanisms through Which the Reactive Metabolite Diclofenac Acyl Glucuronide Can Mediate Toxicity. J Pharmacol Exp Ther. 2016;357(1):167-176.  [Content Brief]

  [2]. Seitz S, et al. Diclofenac acyl glucuronide, a major biliary metabolite, is directly involved in small intestinal injury in rats. Gastroenterology. 1998;115(6):1476-1482.  [Content Brief]