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Current Topics in Medicinal Chemistry

Author(s): Ru Wang, Yi-Ang Wang, Yun-Gen Xu* and Lei Shi*

DOI: 10.2174/1568026622666220209143949

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Privileged Scaffolds Targeting Bromodomain-containing Protein 4

Page: [600 - 627] Pages: 28

  • * (Excluding Mailing and Handling)

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.

Keywords: BRD4, BET, Small molecule inhibitor, Privileged scaffold, Structure-activity relationship, protein.

Graphical Abstract

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