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Advances on Keap1-Nrf2 protein-protein interaction inhibitors and degraders
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Jian-yu YAN, Guo-dong LIU, Zhen-yuan MIAO, Chun-lin ZHUANG*
Acta Pharmaceutica Sinica | 2022, 57(10) : 2932 - 2948
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Acta Pharmaceutica Sinica | 2022, 57(10): 2932-2948
Special Reports Ⅰ: New Targets, New Strategies for Drug Discovery and Advances in Antiviral Drug Research
Advances on Keap1-Nrf2 protein-protein interaction inhibitors and degraders
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Jian-yu YAN, Guo-dong LIU, Zhen-yuan MIAO, Chun-lin ZHUANG*
Affiliations
  • School of Pharmacy, Second Military Medical University, Shanghai 200433, China
Published: 2022-10-12 doi: 10.16438/j.0513-4870.2022-0669
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Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.

oxidative stress  /  nuclear factor E2-related factor 2  /  Kelch like ECH-associated protein 1  /  protein-protein interaction  /  proteolysis targeting chimeras
Jian-yu YAN, Guo-dong LIU, Zhen-yuan MIAO, Chun-lin ZHUANG. Advances on Keap1-Nrf2 protein-protein interaction inhibitors and degraders[J]. Acta Pharmaceutica Sinica, 2022 , 57 (10) : 2932 -2948 . DOI: 10.16438/j.0513-4870.2022-0669
Year 2022 volume 57 Issue 10
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doi: 10.16438/j.0513-4870.2022-0669
  • Receive Date:2022-05-31
  • Online Date:2025-12-24
  • Published:2022-10-12
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  • Received:2022-05-31
  • Revised:2022-06-17
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    School of Pharmacy, Second Military Medical University, Shanghai 200433, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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