Recent Advances in the Development of CBP/p300 Bromodomain Inhibitors
Ying Xiong1, Mingming Zhang2, Yingxia Li2
1Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Abstract:
CBP and p300 are two closely related Histone Acetyltransferases (HATs) that interact with numerous transcription factors and act to increase the expression of their target genes. Both proteins contain a bromodomain flanking the HAT catalytic domain that is important in binding of CBP/p300 to chromatin, which offers an opportunity to develop protein-protein interaction inhibitors. Since their discovery in 2006, CBP/p300 bromodomains have attracted much interest as promising new epigenetic targets for diverse human diseases, including inflammation, cancer, autoimmune disorders, and cardiovascular disease. Herein, we present a comprehensive review of the structure, function, and inhibitors of CBP/p300 bromodomains developed in the last several years, which is expected to be beneficial to relevant studies.
Insights
CBP and p300 proteins, crucial for gene expression, have bromodomains that are promising epigenetic targets. Inhibitors targeting these CBP/p300 bromodomains show potential for treating various human diseases.
Area of Science:
- Biochemistry
- Epigenetics
- Molecular Biology
Background:
- CBP and p300 are related Histone Acetyltransferases (HATs) that regulate gene expression.
- Their bromodomains are critical for chromatin binding and are implicated in various diseases.
- These bromodomains have emerged as significant epigenetic drug targets.
Purpose of the Study:
- To provide a comprehensive review of CBP/p300 bromodomain structure and function.
- To summarize the development of CBP/p300 bromodomain inhibitors.
- To highlight the therapeutic potential of targeting CBP/p300 bromodomains.
Main Methods:
- Literature review of scientific publications.
- Analysis of structural and functional data for CBP/p300 bromodomains.
- Compilation of data on developed small molecule inhibitors.
Main Results:
- Detailed overview of CBP/p300 bromodomain structural features and functional roles.
- Summary of diverse classes of inhibitors targeting CBP/p300 bromodomains.
- Identification of key interactions and inhibition mechanisms.
Conclusions:
- CBP/p300 bromodomains are validated epigenetic targets with significant therapeutic potential.
- Inhibitors targeting these bromodomains offer a promising strategy for treating cancer, inflammation, and autoimmune diseases.
- Further research into CBP/p300 bromodomain inhibitors is warranted for drug development.
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