2. Academic Validation
  3. Upregulation of p53 through induction of MDM2 degradation: Anthraquinone analogs

Upregulation of p53 through induction of MDM2 degradation: Anthraquinone analogs

  • Bioorg Med Chem. 2019 Sep 1;27(17):3860-3865. doi: 10.1016/j.bmc.2019.07.019.
Alexander B Draganov 1,  Xiaoxiao Yang 1,  Abiodun Anifowose 1,  Ladie Kimberly C De La Cruz 1,  Chaofeng Dai 1,  Nanting Ni 1,  Weixuan Chen 1,  Zeus De Los Santos 1,  Lubing Gu 2,  Muxiang Zhou 2,  Binghe Wang 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, United States.
  • 2 Department of Pediatrics and Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA 30322, United States.
  • 3 Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, United States. Electronic address: wang@gsu.edu.
PMID: 31324563 DOI: 10.1016/j.bmc.2019.07.019
Abstract

In a previous study, a novel anthraquinone analog BW-AQ-101 was identified as a potent inducer of MDM2 degradation, leading to upregulation of p53 and Apoptosis in Cell Culture studies. In animal models of acute lymphocytic leukemia, treatment with BW-AQ-101 led to complete disease remission. In this study, we systematically investigated the effect of substitution patterns of the core anthraquinone scaffold. Through cytotoxicity evaluation in two leukemia cell lines, the structure-activity relationship of thirty-two analogs has been examined. Several analogs with comparable or improved potency over BW-AQ-101 have been identified. Western-blot assays verified the effect of the potent compounds on the MDM2-p53 axis. The study also suggests new chemical space for further optimization work.

Keywords

Anthraquinone; Anti-tumor activity; Lymphoblastic leukemia; MDM2 inhibitor; p53 activation.

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