Targeting the epigenetic reader “BET” as a therapeutic strategy for cancer

Wahi, Abhishek; Manchanda, Namish; Jain, Priti; Jadhav, Hemant R

doi:10.1016/j.bioorg.2023.106833

Cited by 4 publications

(4 citation statements)

References 207 publications

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“…The bromodomain and extra‐terminal domain (BET) family serves as an epigenetic reader of post‐translational modifications. Bromodomains (BRDs) specifically recognize acetylated lysine (KAc) in both histone and nonhistone proteins via the BRD [1–4] . The human genome encodes 61 BRDs in 46 different BRD‐containing proteins, and The BET family comprises four members in humans (bromodomain containing 2 protein (BRD2), bromodomain containing 3 protein (BRD3) and bromodomain containing 4 protein (BRD4), and testis‐specific bromodomain (BRDT) [5] …”

Section: Introductionmentioning

confidence: 99%

“…Since BET proteins have been found to play a critical role in the formation of various cancer types, inhibiting the BRD‐histone interaction is seen as a new and attractive pathway in cancer treatment. The structural identification of the hydrophobic pocket in which the KAc‐BRD complex is formed, allows the development of small inhibitor molecules in this context [1,3–7] …”

Section: Introductionmentioning

confidence: 99%

“…Bromodomains (BRDs) specifically recognize acetylated lysine (KAc) in both histone and nonhistone proteins via the BRD. [1][2][3][4] The human genome encodes 61 BRDs in 46 different BRD-containing proteins, and The BET family comprises four members in humans (bromodomain containing 2 protein (BRD2), bromodomain containing 3 protein (BRD3) and bromodomain containing 4 protein (BRD4), and testis-specific bromodomain (BRDT). [5] BET proteins play critical role in most hematological and solid tumors by acting as coactivators in the expression of proliferative genes.…”

Section: Introductionmentioning

confidence: 99%

“…The structural identification of the hydrophobic pocket in which the KAc-BRD complex is formed, allows the development of small inhibitor molecules in this context. [1,[3][4][5][6][7] Flavones are compounds with a benzo-γ-pyrone structure that form the color and odor of vegetables and fruits in nature. There are approximately 9000 different flavonoid derivatives isolated from plants, and people have been consuming plants rich in flavonoids for the treatment of various diseases for years.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

New Flavone Derivatives Targeting BET Proteins in Cancer: Synthesis, Structure Analysis and Investigation of Bromodomain Inhibitory Activities**

Gultekin,

Ozkan,

Bakar‐Ates

et al. 2023

ChemistrySelect

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Bromodomains (BRDs) are key transcriptional regulators that control expression of genes. Dysfunction of BRDs has been associated with the development of aggressive tumors. BRDs have emerged as attractive candidates for the development of inhibitors targeting gene transcription. Flavones can act as a potent anticancer agent. In this paper, a series of ten new flavonylquinazoline sulfonamide compounds (FQ1‐FQ10) was synthesized and their cytotoxicity was investigated in human A549 lung carcinoma, MCF‐7 breast carcinoma ve K562 myeloid leukemia cell lines. The most cytotoxic compounds FQ1 and FQ6 were tested for their bromodomain containing 2 protein (BRD2), bromodomain containing 3 protein (BRD3) and bromodomain containing 4 protein (BRD4) inhibitor activities. The results showed that new FQ1 and FQ6 flavone compounds exhibited BRD2, BRD3 inhibitor activity. We suggest that flavonylquinazoline sulfonamide compounds have the potential to inhibit bromodomain activity, thus may be pharmacologically of interest for further investigations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%