title: Design, Synthesis, and Biological Evaluation of a Series of Anthracene-9,10-dione Dioxime β-Catenin Pathway Inhibitors.
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.
authors.affiliation: †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.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Soldi
authors.affiliation: ‡ Beta Cat Pharmaceuticals LLC, 22 Firstfield Road, Gaithersburg, Maryland 20878, United States.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Horrigan
authors.affiliation: § Park Life Science, Selvita S.A., 30-348 Krakow, Poland.
authors.forename: Marek W
authors.initials: MW
authors.lastname: Cholody
authors.affiliation: ∥PrimeTime Life Sciences, 9700, Great Seneca Highway, Rockville, Maryland 20850, United States.
authors.forename: Janak
authors.initials: J
authors.lastname: Padia
authors.affiliation: †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.
authors.forename: Venkataswamy
authors.initials: V
authors.lastname: Sorna
authors.affiliation: †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.
authors.forename: Jared
authors.initials: J
authors.lastname: Bearss
authors.affiliation: †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.
authors.forename: Glynn
authors.initials: G
authors.lastname: Gilcrease
authors.affiliation: ⊥Cockrell Center for Advanced Therapeutics, The Methodist Hospital Research Institute, 6670 Bertner Avenue, R9-113, Houston, Texas 77030, United States.
authors.forename: Kapil
authors.initials: K
authors.lastname: Bhalla
authors.affiliation: #Department of Pediatric Hematology/Oncology, Primary Children's Hospital, University of Utah, 100 Mario Capecchi Drive, Salt Lake City, Utah 84113, United States.
authors.forename: Anupam
authors.initials: A
authors.lastname: Verma
authors.affiliation: †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.
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Vankayalapati
authors.affiliation: †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.
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D010091:Oximes; D051176:beta Catenin