Coelenterazine

Target: superoxide anion

IC50: 69 μM (rat hepatocytes cells)

The small molecule coelenterazine, a luminescent enzyme substrate, can react with the reactive oxygen species (ROS) superoxide anion and peroxynitrite and produce a chemiluminescent signal [1]. Therefore, coelenterazine is used for monitoring reporter genes in ELISA, BRET, and HTS techniques. Reactive oxygen species (ROS) play an important role in tumor development and survival and it is a new treatment strategy to target the cancer-specific ROS.

In vitro: Coelenterazine showed antioxidative properties in primary cultures of rat hepatocytes subjected to the oxidant tert-butyl hydroperoxide (t-BHP). Coelenterazine (3-10 μM) concentration-dependently increased survival and decreased lipid peroxidation in rat hepatocytes treated for 6 hr with t-BHP (250 μM) [2]. In addition, Coelenterazine (10 μmol/l) can be used to assay superoxide anion concentrations in cancer cell lines [1].

In vivo: the small molecule coelenterazine (5 mg/kg, intravenous administration) was a potential reporter of cancer-associated superoxide anion in the 4T1 breast adenocarcinoma mouse model [1]. Gli36-Rluc or Gli36-Gluc cells were injected into the leg muscle of nude mice. The mice were injected with 4 mg/kg of coelenterazine and imaged by a cooled charge-coupled device camera [3].

References:
1.  Bronsart LL, Stokes C, Contag CH. Multimodality Imaging of Cancer Superoxide Anion Using the Small Molecule Coelenterazine. Mol Imaging Biol. 2016;18(2):166-71.
2.  Dubuisson ML, de Wergifosse B, Trouet A, Baguet F, Marchand-Brynaert J, Rees JF. Antioxidative properties of natural coelenterazine and synthetic methyl coelenterazine in rat hepatocytes subjected to tert-butyl hydroperoxide-induced oxidative stress. Biochem Pharmacol. 2000;60(4):471-8.
3.  Morse D, Tannous BA. A water-soluble coelenterazine for sensitive in vivo imaging of coelenterate luciferases. Mol Ther. 2012;20(4):692-3.