NRF2 inhibitors: Recent progress, future design and therapeutic potential

• Published in: European journal of medicinal chemistry Vol. 279; p. 116822
• Main Authors: Lv, Bingbing, Xing, Shuaishuai, Wang, Zhiqiang, Zhang, Ao, Wang, Qinjie, Bian, Yaoyao, Pei, Yuqiong, Sun, Haopeng, Chen, Yao
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 05-12-2024
• Subjects: Chemotherapy resistance; NRF2 inhibitors; NRF2-KEAP1 signaling; NRF2 inhibitors; NRF2-KEAP1 signaling; Chemotherapy resistance
• ISSN: 0223-5234; 1768-3254; 1768-3254
• DOI: 10.1016/j.ejmech.2024.116822

Nuclear factor erythroid 2-related factor 2 (NRF2) is a crucial transcription factor involved in oxidative stress response, which controls the expression of various cytoprotective genes. Recent research has indicated that constitutively activated NRF2 can enhance patients' resistance to chemotherapy drugs, resulting in unfavorable prognosis. Therefore, the development of NRF2 inhibitors has emerged as a promising approach for overcoming drug resistance in cancer treatment. However, there are limited reports and reviews focusing on NRF2 inhibitors. This review aims to provide a comprehensive analysis of the structure and regulation of the NRF2 signaling pathway, followed by a comprehensive review of reported NRF2 inhibitors. Moreover, the current design strategies and future prospects of NRF2 inhibitors will be discussed, aiming to establish a foundation for the development of more effective NRF2 inhibitors.
[Display omitted]
•NRF2 has a dual effect in the process of carcinogenesis.•Inhibiting NRF2 is a promising strategy for addressing drug resistance in cancer.•This review summarizes recent advances in potential NRF2 inhibitors.•The obstacles and the potential direction of NRF2 inhibitors were proposed in this review.