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A novel 2-oxopyrrolidine derivative (LN-53) efficiently induces Nrf-2 signaling pathway activation in human epidermal keratinocytes

Laura Nissim, Basak Ezgi Sarac, Dilara Karaguzel, Gokhan Arik, Shirin Kahremany, Edward E. Korshin, Arie Gruzman & Cagatay Karaaslan , 2025

The skin is a pivotal organ that serves as a physical barrier, protecting the body from harmful substances such as pathogens, allergens, and other environmental irritants. Chronic inflammation in the skin, along with the anthropogenic effects, can cause reactive oxygen species (ROS) overproduction. Prolonged exposure to elevated ROS levels and inadequate antioxidant defenses in the skin can contribute to the onset of various skin disorders. The nuclear factor erythroid 2-related factor-2 (Nrf-2) signaling pathway plays a key role in enhancing antioxidant capacity by promoting the production of antioxidant and detoxifying molecules. Consequently, pharmacological activation of the Nrf-2 pathway may help restore the oxidant-antioxidant balance, thereby improving therapeutic outcomes for chronic skin disorders. This study aimed to investigate the potential effect of novel agent: (5-((4-(4-(methoxycarbonyl)-2-oxopyrrolidin-1-yl)phenyl)carbamoyl)benzene-1,2,3-triyl triacetate (LN-53), synthesized based on the structure of previously developed by our team lead compound SK-119, on Nrf-2 signaling pathway in human epidermal keratinocytes (HEKs) at mRNA and protein level.