Discovery and Development of Kelch-like ECH-Associated Protein 1. Nuclear Factor Erythroid 2‑Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction Inhibitors: Achievements, Challenges, and Future Directions
The transcription factor Nrf2 is the primary regulator of the cellular defense system, and enhancing Nrf2 activity has potential usages in various diseases, especially chronic age-related and inflammatory diseases. Recently, directly targeting Keap1–Nrf2 protein–protein interaction (PPI) has been an...
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| Published in | Journal of medicinal chemistry Vol. 59; no. 24; pp. 10837 - 10858 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
22.12.2016
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The transcription factor Nrf2 is the primary regulator of the cellular defense system, and enhancing Nrf2 activity has potential usages in various diseases, especially chronic age-related and inflammatory diseases. Recently, directly targeting Keap1–Nrf2 protein–protein interaction (PPI) has been an emerging strategy to selectively and effectively activate Nrf2. This Perspective summarizes the progress in the discovery and development of Keap1–Nrf2 PPI inhibitors, including the Keap1–Nrf2 regulatory mechanisms, biochemical techniques for inhibitor identification, and approaches for identifying peptide and small-molecule inhibitors, as well as discusses privileged structures and future directions for further development of Keap1–Nrf2 PPI inhibitors. |
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| AbstractList | The transcription factor Nrf2 is the primary regulator of the cellular defense system, and enhancing Nrf2 activity has potential usages in various diseases, especially chronic age-related and inflammatory diseases. Recently, directly targeting Keap1-Nrf2 protein-protein interaction (PPI) has been an emerging strategy to selectively and effectively activate Nrf2. This Perspective summarizes the progress in the discovery and development of Keap1-Nrf2 PPI inhibitors, including the Keap1-Nrf2 regulatory mechanisms, biochemical techniques for inhibitor identification, and approaches for identifying peptide and small-molecule inhibitors, as well as discusses privileged structures and future directions for further development of Keap1-Nrf2 PPI inhibitors. |
| Author | Jiang, Zheng-Yu You, Qi-Dong Lu, Meng-Chen |
| AuthorAffiliation | China Pharmaceutical University State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization Department of Medicinal Chemistry, School of Pharmacy |
| AuthorAffiliation_xml | – name: State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization – name: China Pharmaceutical University – name: Department of Medicinal Chemistry, School of Pharmacy |
| Author_xml | – sequence: 1 givenname: Zheng-Yu surname: Jiang fullname: Jiang, Zheng-Yu – sequence: 2 givenname: Meng-Chen surname: Lu fullname: Lu, Meng-Chen – sequence: 3 givenname: Qi-Dong surname: You fullname: You, Qi-Dong email: youqidong@gmail.com |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27690435$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Animals Drug Discovery Humans Kelch-Like ECH-Associated Protein 1 - antagonists & inhibitors NF-E2-Related Factor 2 - antagonists & inhibitors Protein Binding - drug effects Small Molecule Libraries - chemistry Small Molecule Libraries - pharmacology |
| Title | Discovery and Development of Kelch-like ECH-Associated Protein 1. Nuclear Factor Erythroid 2‑Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction Inhibitors: Achievements, Challenges, and Future Directions |
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