TY - JOUR
T1 - Design, Synthesis, and Biological Evaluation of a Series of Anthracene-9,10-dione Dioxime β-Catenin Pathway Inhibitors
AU - Soldi, Raffaella
AU - Horrigan, Stephen K.
AU - Cholody, Marek W.
AU - Padia, Janak
AU - Sorna, Venkataswamy
AU - Bearss, Jared
AU - Gilcrease, Glynn
AU - Bhalla, Kapil
AU - Verma, Anupam
AU - Vankayalapati, Hariprasad
AU - Sharma, Sunil
N1 - Publisher Copyright:
© 2015 American Chemical Society.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2015/7/16
Y1 - 2015/7/16
N2 - 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.
AB - 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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U2 - 10.1021/acs.jmedchem.5b00460
DO - 10.1021/acs.jmedchem.5b00460
M3 - Article
AN - SCOPUS:84939193324
VL - 58
SP - 5854
EP - 5862
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 15
ER -