Histone acetyltransferase inhibitors: An overview in synthesis, structure-activity relationship and molecular mechanism
- Eur J Med Chem. 2019 Sep 15:178:259-286. doi: 10.1016/j.ejmech.2019.05.078.
- 1. State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
- 2. Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
- 3. State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China. Electronic address: [email protected].
Acetylation, a key component in post-translational modification regulated by HATs and HDACs, is relevant to many crucial cellular contexts in organisms. Based on crucial pharmacophore patterns and the structure of targeted proteins, HAT inhibitors are designed and modified for higher affinity and better bioactivity. However, there are still some challenges, such as cell permeability, selectivity, toxicity and synthetic availability, which limit the improvement of HAT inhibitors. So far, only few HAT inhibitors have been approved for commercialization, indicating the urgent need for more successful and effective structure-based drug design and synthetic strategies. Here, we summarized three classes of HAT inhibitors based on their sources and structural scaffolds, emphasizing on their synthetic methods and structure-activity relationships and molecular mechanisms, hoping to facilitate the development and further application of HAT inhibitors.