2. Academic Validation
  3. Design, Synthesis, and Biological Evaluation of a Series of Anthracene-9,10-dione Dioxime β-Catenin Pathway Inhibitors

Design, Synthesis, and Biological Evaluation of a Series of Anthracene-9,10-dione Dioxime β-Catenin Pathway Inhibitors

  • J Med Chem. 2015 Aug 13;58(15):5854-62. doi: 10.1021/acs.jmedchem.5b00460.
Raffaella Soldi 1,  Stephen K Horrigan 2,  Marek W Cholody 3,  Janak Padia 4,  Venkataswamy Sorna 1,  Jared Bearss 1,  Glynn Gilcrease 1,  Kapil Bhalla 5,  Anupam Verma 6,  Hariprasad Vankayalapati 1,  Sunil Sharma 1
Affiliations

Affiliations

  • 1 †Division of Oncology of School of Medicine and Center for Investigational Therapeutics at Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, Utah 84112, United States.
  • 2 ‡ Beta Cat Pharmaceuticals LLC, 22 Firstfield Road, Gaithersburg, Maryland 20878, United States.
  • 3 § Park Life Science, Selvita S.A., 30-348 Krakow, Poland.
  • 4 ∥PrimeTime Life Sciences, 9700, Great Seneca Highway, Rockville, Maryland 20850, United States.
  • 5 ⊥Cockrell Center for Advanced Therapeutics, The Methodist Hospital Research Institute, 6670 Bertner Avenue, R9-113, Houston, Texas 77030, United States.
  • 6 #Department of Pediatric Hematology/Oncology, Primary Children's Hospital, University of Utah, 100 Mario Capecchi Drive, Salt Lake City, Utah 84113, United States.
PMID: 26182238 DOI: 10.1021/acs.jmedchem.5b00460
Abstract

The Wnt/β-catenin signaling pathway plays a vital role in cell growth, the regulation, cell development, and the differentiation of normal stem cells. Constitutive activation of the Wnt/β-catenin signaling pathway is found in many human cancers, and thus, it is an attractive target for Anticancer therapy. Specific inhibitors of this pathway have been keenly researched and developed. Cell based screening of compounds library, hit-to-lead optimization, computational and structure-based design strategies resulted in the design and synthesis of a series of anthracene-9,10-dione dioxime series of compounds demonstrated potent inhibition of β-catenin in vitro (IC50 < 10 nM, 14) and the growth of several Cancer cell lines. This article discusses the potential of inhibiting the Wnt/β-catenin signaling pathway as a therapeutic approach for Cancer along with an overview of the development of specific inhibitors.

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