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Sulfonamide Inhibitors of β‐Catenin Signaling as Anticancer Agents with Different Output on c‐MYC
Author(s) -
Di Magno Laura,
Di Pastena Fiorella,
Puxeddu Michela,
La Regina Giuseppe,
Coluccia Antonio,
Ciogli Alessia,
Manetto Simone,
Maroder Marella,
Canettieri Gianluca,
Silvestri Romano,
Nalli Marianna
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000594
Subject(s) - wnt signaling pathway , chemistry , catenin , signal transduction , cell growth , cancer research , pharmacology , biology , biochemistry
The Wnt/β‐catenin pathway is often found deregulated in cancer. The aberrant accumulation of β‐catenin in the cell nucleus results in the development of various malignancies. Specific drugs against this signaling pathway for clinical treatments have not been approved yet. Herein we report inhibitors of β‐catenin signaling of potential therapeutic value as anticancer agents. Ethyl 4‐((4‐(trifluoromethyl)phenyl)sulfonamido)benzoate (compound 14 ) inhibits the effect on Wnt reporter with an IC 50 value of 7.0 μM, significantly reduces c‐MYC levels, inhibits HCT116 colon cancer cell growth (IC 50 20.2 μM), does not violate Lipinski and Veber rules, and shows predicted Caco‐2 and MDCK cell permeability P app >500 nm s −1 . Compound 14 seems to have potential for the development of new anticancer therapies.