In this review, we describe the pharmacological activators of NRF2 that are in several stages of pharmacological development for the treatment of several chronic diseases. The most developed compounds activate NRF2 by preventing its degradation by KEAP1-dependent mechanisms.

2022年6月30日 · Transient Nrf2 activation, by its specific activators, has protective roles against carcinogenesis and cancer development. However, permanent activation of Nrf2 promotes various cancer properties, comprising malignant progression, chemo/radio resistance, and poor patient prognosis.

NRF2 activators initiate a protective cellular response by engaging with the NRF2 pathway, thereby enhancing the body's defense against oxidative stress and inflammation. When you dive deeper into the activation mechanisms, you'll find that NRF2 activators work by detaching NRF2 from its inhibitor, KEAP1.

2023年3月1日 · Several small-molecule NRF2 activators are currently in clinical trials in different disease settings, and one such compound, dimethyl fumarate, is licensed for the treatment of remitting-relapsing multiple sclerosis (RRMS) and psoriasis.

2019年7月14日 · This review describes the electrophilic and nonelectrophilic NRF2 activators with clinical projection in various chronic diseases. We also analyze the status of NRF2 inhibitors, which at this time provide proof of concept for blocking NRF2 activity in cancer therapy.

Interestingly, different natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response associated with the beneficial effects against stroke. According to several studies, the combination of different bioactive compounds can lead to a better neuroprotection.

2024年9月20日 · Molecular Mechanisms of NRF2 Activation. The activation of NRF2 is a finely tuned process that involves a series of molecular interactions and modifications. Under normal conditions, NRF2 is bound to its inhibitor, KEAP1, in the cytoplasm.

2021年11月29日 · NRF2 activators prevent excessive cellular damage produced by metabolic, xenobiotic and oxidative stress; thus, they may play an important role in cancer chemoprevention.

2015年10月20日 · In this work, we have developed a comprehensive structure-activity relationship around a known, naphthalene-based non-electrophilic activator of Nrf2, and we report highly potent non-electrophilic activators of Nrf2.

2022年6月30日 · By inducing several cytoprotective and detoxifying gene expressions, Nrf2 can increase the sensitivity of the cells to oxidants and electrophiles. Transient Nrf2 activation, by its specific activators, has protective roles against carcinogenesis and cancer development.