Gerets, Helga H. J. published the artcileInvestigation of the Nrf2 Stress Response at Cellular Level to Detect Compounds Inducing Oxidative and Electrophilic Stress, Formula: C13H8Cl2O4S, the main research area is Nrf2 oxidative electrophilic stress liver injury.
Drug-induced liver injury (DILI) remains a significant reason for drug attrition and withdrawal. DILI can be caused by several mechanisms, one of these is the formation of reactive metabolites (RM) leading to oxidative and electrophilic stress. Since such event activates NF-E2-related factor-2 (Nrf2) and its downstream pathways, it seems relevant to measure Nrf2 activation. In this article, Nrf2 activation was evaluated using two approaches. First, three human hepatocytes donors and HepG2 cells were exposed to five compounds known to produce RM- and four non-RM forming compounds The expression of seven genes under the regulation of Nrf2 was measured. An index was calculated taking into account the results of the seven genes. Subsequently, the mean index for the RM-forming and the non-RM-forming compounds was calculated for each donor, and the midpoint between these two values was determined, which represents the donor-specific threshold and the compounds were classified accordingly. All three donors obtained a sensitivity of 80% (4/5) and a specificity between 75% (3/4) and 100% (4/4). HepG2 cells obtained 80% (4/5) sensitivity, but very poor specificity 0% (0/4), which makes them less suitable, compared to human hepatocytes donors, for screening of electrophilic stress. Second, the Antioxidant-Response-Element-Reporter-Cell Line, AREc32, was exposed to the same set of compounds in addition to 13 RM-forming and 5 non-RM-forming compounds Using an arbitrary cutoff of 1.5, a sensitivity of 78% (14/18) and a specificity of 88% (7/8) were obtained. Acceptable predictive values and easiness of use make the AREC32 assay more suited to investigate Nrf2 activation compared to the first approach.
Applied In Vitro Toxicology published new progress about Cell line (AREc32). 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Formula: C13H8Cl2O4S.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem