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Novel BRD4-p53 Inhibitor SDU-071 Suppresses Proliferation and Migration of MDA-MB-231 Triple-Negative Breast Cancer Cells.

Author information

Affiliations

  • 1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
      Authors
    • Wang S 1
    • Lei K 1
    • Liu T 1
    • Du L 1
    • Ye X 1
    • Li M 1
    (6 authors)
  • 2. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
      Authors
    • Lai HT 2
    • Wu SY 2
    • Chiang CM 2
    (3 authors)

ORCIDs linked to this article

ACS Pharmacology & Translational Science, 12 Mar 2024, 7(4):1178-1190
https://doi.org/10.1021/acsptsci.4c00057 PMID: 38633583 

Free full text available after 12 Mar 2025

Abstract 

A promising alternative for cancer treatment involves targeted inhibition of the epigenetic regulator bromodomain-containing protein 4 (BRD4); however, available BRD4 inhibitors are constrained by their potency, oral bioavailability, and cytotoxicity. Herein, to overcome the drawback of the translational BRD4 inhibitors, we describe a novel BRD4-p53 inhibitor, SDU-071, which suppresses BRD4 interaction with the p53 tumor suppressor and its biological activity in MDA-MB-231 triple-negative breast cancer (TNBC) cells in vitro and in vivo. This novel small-molecule BRD4-p53 inhibitor suppresses cell proliferation, migration, and invasion by downregulating the expression of BRD4-targeted genes, such as c-Myc and Mucin 5AC, and inducing cell cycle arrest and apoptosis, as demonstrated in cultured MDA-MB-231 TNBC cells. Its antitumor activity is illustrated in an orthotopic mouse xenograft mammary tumor model. Overall, our results show that SDU-071 is a viable option for potentially treating TNBC as a new BRD4-p53 inhibitor.

Full text links 

Read article at publisher's site: https://doi.org/10.1021/acsptsci.4c00057

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Funding 

Funders who supported this work.

NCI NIH HHS (1)