Nrf2 is a key player in the endogenous protective mechanism of the skin. Its activation might be beneficial for the positive effect on the numerous health-related disorders, including skin sensitization, oxidative imbalance, premature extrinsic aging and skin inflammation. We developed several Nrf-2 activators based on the in silico methods. Several compounds were able to attenuate key pathways underlying skin damage, including block of cytosolic and mitochondrial reactive oxygen species (ROS) generation. Their effect was independent from the direct scavenging ability of the compounds. In addition, several compounds were able to reduce IL-8 hypersecretion from keratinocytes in pharmacologically relevant concentrations. Lastly, the safety and the efficacy of developed in our lab Nrf-2 inhibitors were evaluated and

demonstrated in the ex vivo human skin organ culture model. Now several such compounds are under investigation in Skin Disease Dead Sea Research Center.