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Privileged Scaffolds Targeting Bromodomain-containing Protein 4
Ru Wang1, Yi-Ang Wang1, Yun-Gen Xu1
1Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China.
Abstract:
In recent years, bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra terminal domain (BET) family, has been one of the most widely studied targets. BRD4 is a transcriptional regulation factor, which regulates cell transcription, marks mammalian biological mitosis, regulates cell cycle, and plays an important role in the biological process of cancer occurrence and development. It has been demonstrated that the imbalance or dysfunction of BRD4 expression leads to various types of cancers, including testicular gene nuclear protein melanoma, acute myeloid leukemia, colon cancer, breast cancer, liver cancer, and midline cancer. Therefore, inhibition of BRD4 has become a valuable approach in the treatment of these cancers. To date, there are numerous BRD4 inhibitors in preclinical development, some of which have entered human clinical trials. In this review, current progress in the development of privileged scaffolds designed as BRD4 inhibitors will be discussed by focusing on structure-activity relationship, selectivity, and mechanisms of action.
Insights
Bromodomain-containing protein 4 (BRD4) is a key factor in cancer development. Inhibiting BRD4 shows promise for treating various cancers, with many new drugs in development and clinical trials.
Area of Science:
- Molecular Biology
- Oncology
- Drug Discovery
Background:
- Bromodomain-containing protein 4 (BRD4), a BET family member, is crucial for transcriptional regulation, cell cycle, and mitosis.
- Dysregulated BRD4 expression is implicated in diverse cancers, including leukemia, melanoma, and liver cancer.
Purpose of the Study:
- This review focuses on the development of privileged scaffolds as BRD4 inhibitors.
- It examines structure-activity relationships, selectivity, and mechanisms of action for these inhibitors.
Main Methods:
- Literature review of current research on BRD4 inhibitors.
- Analysis of structure-activity relationships and selectivity profiles.
- Discussion of mechanisms of action for identified inhibitors.
Main Results:
- Numerous BRD4 inhibitors are in preclinical development.
- Several BRD4 inhibitors have advanced to human clinical trials.
- Privileged scaffolds are being actively explored for targeted cancer therapy.
Conclusions:
- BRD4 inhibition is a promising therapeutic strategy for various cancers.
- Continued research into BRD4 inhibitors is essential for advancing cancer treatment.
- Understanding structure-activity relationships and selectivity is key to developing effective drugs.
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