Review
Pharmacology & Pharmacy
Daniela Maria Tanase, Alina Georgiana Apostol, Claudia Florida Costea, Claudia Cristina Tarniceriu, Ionut Tudorancea, Minela Aida Maranduca, Mariana Floria, Ionela Lacramioara Serban
Summary: Arterial hypertension is a prevalent disease characterized by increased incidence and heterogeneous pathophysiology. Oxidative stress plays an important role in its development, with excessive levels causing vascular cell damage and promoting hypertension. Transcription factors such as Nrf2 mediate antioxidant response pathways and provide protection.
Article
Fisheries
Yun Wang, Yafei Duan, Jianhua Huang, Jun Wang, Chuanpeng Zhou, Shigui Jiang, Heizhao Lin, Zhe Zhang
Summary: PmNrf2, a member of CNC-bZIP transcription factor family, is constitutively expressed in various tissues of shrimp and responds to bacterial challenge. Knockdown of PmNrf2 results in decreased expression of PmGPx gene, indicating its role in regulating the transcription of antioxidant enzyme genes in shrimp.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Article
Oncology
Yanqiong Liu, Qiulian Wu, Fuyong Zhang, Xue Qin
Summary: This study provides evidence for the first time that the NRF2 gene rs6721961 variation is a potential genetic marker for susceptibility to hepatocellular carcinoma (HCC).
CANCER CELL INTERNATIONAL
(2023)
Review
Cell Biology
Rabab S. Hamad, Hayder M. Al-kuraishy, Athanasios Alexiou, Marios Papadakis, Eman A. Ahmed, Hebatallah M. Saad, Gaber El-Saber Batiha
Summary: COVID-19 is a recent pandemic caused by SARS-CoV-2, leading to pulmonary and extra-pulmonary manifestations. Inhibition of Nrf2 may contribute to oxidative stress and hyperinflammation in COVID-19. Nrf2 pathway suppresses pro-inflammatory cytokines, reducing pulmonary symptoms. Nrf2 activators can improve endothelial dysfunction, RAS dysregulation, immune thrombosis, and coagulopathy.
CELL STRESS & CHAPERONES
(2023)
Article
Genetics & Heredity
Yusuf Ayikgoz, Mehmet Salih Aydin, Nazim Kankilic, Ebru Temiz
Summary: During cardiopulmonary bypass, TNF-alpha, Nrf2, and HO-1 gene expressions increase, and these values decrease postoperatively. This indicates that oxidative stress and inflammatory processes start with cardiopulmonary bypass, and antioxidant processes start similarly.
Article
Gastroenterology & Hepatology
Shuang Zhao, Tianyu Song, Yue Gu, Yihua Zhang, Siyi Cao, Qing Miao, Xiyue Zhang, Hongshan Chen, Yuanqing Gao, Lei Zhang, Yi Han, Hong Wang, Jun Pu, Liping Xie, Yong Ji
Summary: The study suggests that H2S alleviates liver damage by activating Keap1 S-sulfhydration and promoting the activation of Nrf2, leading to increased expression of antioxidant proteins, which may have potential therapeutic benefits for liver diseases.
Review
Pharmacology & Pharmacy
Xue-Ling Wang, Michael Schnoor, Lei-Miao Yin
Summary: MT-2 was initially discovered to be involved in zinc homeostasis and cadmium detoxification, but it has recently gained attention for its altered expression in diseases such as asthma and cancers. Pharmacological strategies have been developed to target MT-2, indicating its potential as a drug target for various diseases. This review highlights recent advances in understanding the protein structure, regulation, binding partners, and new functions of MT-2 in inflammatory diseases and cancers.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Immunology
Wenting Jian, Huigai Ma, Dingming Wang, Peng Yang, Mengbi Jiang, Yu Zhong, Xiang Long, Jingjing Jiang, Yuan Gong
Summary: This study demonstrates that omaveloxolone exerts significant cardioprotective effects in treating sepsis-induced cardiomyopathy by activating the Nrf2 signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Laura Janko, Emese Toth, Miklos Laczik, Boglarka Rauch, Eszter Janka, Balint L. Balint, Peter Bai
Summary: PARP2 plays a role in DNA repair and has regulatory functions in mitochondrial and lipid metabolism. It is also involved in the adverse effects of pharmacological PARP inhibitors. Silencing of PARP2 affects the subcellular localization of NRF2, a regulator of cellular antioxidant defense, and leads to changes in the expression of genes encoding proteins with antioxidant function.
SCIENTIFIC REPORTS
(2023)
Review
Gastroenterology & Hepatology
Dan-Dan Zhu, Xue-Mei Tan, Li-Qing Lu, Si-Jia Yu, Ru-Li Jian, Xin-Fang Liang, Yi-Xuan Liao, Wei Fan, Luciia Barbier-Torres, Austin Yang, He-Ping Yang, Ting Liu
Summary: COVID-19 caused by SARS-CoV-2 is a global pandemic that not only affects respiratory system but also leads to systemic inflammation and liver damage. NRF2 plays a crucial role in regulating antioxidant proteins in the context of COVID-19-induced inflammation and liver injury.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Environmental Sciences
Yuan-yuan Wei, Hui-ru Wang, Yi-meng Fan, Jin-hua Gu, Xiu-ying Zhang, Xu-hao Gong, Zhi-hui Hao
Summary: The study evaluated the effect and underlying mechanism of GDK aqueous extract in alleviating acute liver injury caused by CCl4. The results showed that GDK effectively inhibited liver damage and restored the structure and function of the liver. It achieved this by suppressing liver fibrosis, blocking the NFicB pathway, inhibiting hepatic inflammatory response, reducing oxidative stress, inhibiting ferroptosis, and alleviating hepatocyte injury caused by CCl4. In conclusion, this study provides insights into the potential complex mechanism of GDK against acute liver injury.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Review
Medicine, Research & Experimental
Marjan Talebi, Mohammad Mehdi Sadoughi, Seyed Abdulmajid Ayatollahi, Elaheh Ainy, Roghayeh Kiani, Alireza Zali, Mirmohammad Miri
Summary: CBD, a non-psychoactive cannabinoid, has been found to have numerous therapeutic benefits and is closely associated with the Nrf2 signaling pathway. Nrf2 is linked to various health issues including cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Understanding the relationship between CBD and Nrf2 is of great interest in the medical field and could significantly impact the treatment and prevention of a wide range of health conditions.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Dinh Hoa Hoang, Ralf Buettner, Melissa Valerio, Lucy Ghoda, Bin Zhang, Ya-Huei Kuo, Steven T. Rosen, John Burnett, Guido Marcucci, Vinod Pullarkat, Le Xuan Truong Nguyen
Summary: This study found that the combination of arsenic trioxide (ATO) and Venetoclax (VEN) synergistically induced apoptosis of leukemia stem cells (LSCs) in patients with acute myeloid leukemia (AML), by potentiating the induction of reactive oxygen species (ROS) and inhibiting the Nrf2 antioxidant pathway. This suggests that ATO+VEN could be a promising regimen for treating VEN-sensitive and -resistant AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Huiyan Deng, Miaojian Wan, Huaping Li, Quan Chen, Runxiang Li, Bihua Liang, Huilan Zhu
Summary: The study demonstrates that curcumin can protect the skin from UV damage by regulating the Nrf2 pathway. UV irradiation leads to cell apoptosis and oxidative stress, which can be reversed by adding curcumin. Additionally, curcumin induces Nrf2 nuclear accumulation in Hacat cells to provide protection against UV exposure-induced photodamage.
Article
Plant Sciences
Chuanhong Wu, Feipeng Duan, Ruocong Yang, Yaolan Dai, Xiuping Chen, Shaojing Li
Summary: This study found that 15, 16-Dihydrotanshinone I (DHT) can protect against ferroptosis and ischemic stroke by activating the Nrf2 signaling pathway.
Review
Pharmacology & Pharmacy
Lei Wang, Xiaoli Xu, Zhengyu Jiang, Qidong You
ACTA PHARMACEUTICA SINICA B
(2020)
Review
Chemistry, Medicinal
Mengmin Tao, Tian Liu, Qidong You, Zhengyu Jiang
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Lv-Bin Hu, Xiu-Qi Hu, Qiong Zhang, Qi-Dong You, Zheng-Yu Jiang
Summary: Protein-protein interactions are crucial for cellular processes, and studying them using peptide motifs and computational methods can provide valuable insights for the development of small molecule inhibitors. In this study, a new 6-mer motif with significantly enhanced affinity was discovered for Cbl-b and phosphorylated substrates, demonstrating the importance of structural optimization and activity enhancement mechanisms for PPI blockers.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Xue Li, Junwei Dou, Qidong You, Zhengyu Jiang
Summary: Bfl-1, an important anti-apoptotic protein, lacks developed inhibitors with ideal activity and selectivity, and its therapeutic potential is yet to be fully explored.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Tian Liu, Yi-Fei Lv, Jing-Long Zhao, Qi-Dong You, Zheng-Yu Jiang
Summary: NRF2 is involved in antioxidant pathways and physiological processes, dysregulation is linked to diseases, phosphorylation by kinases is critical in regulating NRF2 activity. Various kinases positively or negatively regulate NRF2 activity through phosphorylation of different sites.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Chemistry, Medicinal
Peng-Ju Zhu, Ze-Zhou Yu, Yi-Fei Lv, Jing-Long Zhao, Yuan-Yuan Tong, Qi-Dong You, Zheng-Yu Jiang
Summary: The study describes the rational design, synthesis, and structure-activity relationships of Mcl-1 inhibitors. The most potent compound 40 showed high affinity and superior selectivity for Mcl-1, activating the apoptosis signal pathway in an Mcl1-dependent manner.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Weilin Chen, Xin Chen, Dongdong Li, Jianrui Zhou, Zhengyu Jiang, Qidong You, Xiaoke Guo
Summary: The WDR5-MLL1 inhibitor compound 63 (DDO-2213) presented potent inhibitory effects and in vivo efficacy, showing potential for treating MLL-rearranged cancers.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Chemistry, Medicinal
Yi Mou, Shuai Wen, Xinxing Gao, Zheng-Yu Jiang
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jianai Ji, Sinan Ma, Yuxuan Zhu, Jinglong Zhao, Yuanyuan Tong, Qidong You, Zhengyu Jiang
Summary: PROTAC technology is a potential strategy to degrade undruggable proteins. By constructing a new Nrf2 degrader called C2, the Nrf2-MafG heterodimer was selectively degraded, leading to the inhibition of Nrf2 transcriptional activity and improved sensitivity of NSCLC cells to ferroptosis and therapeutic drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zheng-Yu Jiang, Qi-Dong You, Xiao-Li Xu, Nan-Nan Chen, Han Zhang, Qiang-Sheng Zhu, Ting Zeng, Wei Dai, Ye-Ling Zhou, Guo-Feng Xin, Bei-Duo Wu, Si-Jia Gong
Summary: By modifying and optimizing the structure of mono-aminobenzimidazole (ABZI), nanomolar STING agonists were obtained. Compounds D59 and D61 significantly increased the transcription of IFN-beta and CXCL10, and induced phosphorylation of STING downstream proteins in THP1 cells. Furthermore, compound D61 exhibited favorable pharmacokinetic properties and effectively inhibited tumor growth in a mouse tumor model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yuhui Jin, Jing Fan, Ruyan Wang, Xuanyu Wang, Ning Li, Qidong You, Zhengyu Jiang
Summary: Event-driven bifunctional molecules, such as PROTAC technology, have been successfully used to degrade proteins of interest (POI). In this study, we propose a versatile ligation to scavenging approach to terminate event-driven degradation. This approach utilizes a TCO-modified dendrimer and tetrazine-modified PROTACs to rapidly scavenge intra-cellular free PROTACs and halt the degradation of specific proteins in living cells. This work presents a flexible chemical knockdown approach for controlling the levels of POI in living cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Xian Zhang, Keni Cui, Xiaolu Wang, Yuanyuan Tong, Chihong Liu, Yuechao Zhu, Qidong You, Zhengyu Jiang, Xiaoke Guo
Summary: Ulcerative colitis (UC) is an inflammatory disease with unknown cause that may be related to intestinal inflammation and oxidative stress. The molecular hybridization of two drug fragments represents a novel strategy for achieving a common pharmacological goal. This study synthesized a series of hybrid derivatives by combining an inhibitor of the Keap1-Nrf2 pathway with two established H2S-donor moieties, resulting in a drug candidate (DDO-1901) that showed a more potent therapeutic effect for UC treatment by improving defense against oxidative stress and reducing inflammation.
Article
Chemistry, Medicinal
Ziquan Zhao, Ruitian Dong, Qidong You, Zhengyu Jiang
Summary: Oxidative stress is associated with various pathological conditions, and the transcription factor Nrf2 plays a crucial role in regulating cellular defense against oxidative and electrophilic damage. Inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 through non-electrophilic means has emerged as a promising approach to activate Nrf2. Recent advances in drug discovery have led to the development of small-molecule Keap1-Nrf2 PPI inhibitors with potent activity and favorable drug-like properties. This Perspective summarizes the latest progress in this field and discusses future prospects and challenges.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Ziquan Zhao, Ruitian Dong, Keni Cui, Qidong You, Zhengyu Jiang
Summary: The Nrf2 pathway plays a crucial role in protecting cells against oxidative stress, and activating this pathway has potential therapeutic implications for oxidative stress-related chronic diseases. This review summarizes the biological effects of Nrf2, the regulatory mechanism of the Keap1-Nrf2-ARE pathway, and the development of Nrf2 activators.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Biochemistry & Molecular Biology
Li Li, Nannan Chen, Dandan Xia, Shicheng Xu, Wei Dai, Yuanyuan Tong, Lei Wang, Zhengyu Jiang, Qidong You, Xiaoli Xu
Summary: The study identified DDO-6600 as a covalent modifier of Hsp90, which inhibits tumor cell proliferation, induces apoptosis, and reduces cell motility.
CELL CHEMICAL BIOLOGY
(2021)