1. Academic Validation
  2. Amide derivatives of ethacrynic acid: synthesis and evaluation as antagonists of Wnt/beta-catenin signaling and CLL cell survival

Amide derivatives of ethacrynic acid: synthesis and evaluation as antagonists of Wnt/beta-catenin signaling and CLL cell survival

  • Bioorg Med Chem Lett. 2009 Feb 1;19(3):606-9. doi: 10.1016/j.bmcl.2008.12.067.
Guangyi Jin 1 Desheng Lu Shiyin Yao Christina C N Wu Jerry X Liu Dennis A Carson Howard B Cottam
Affiliations

Affiliation

  • 1 Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093-0820, USA.
Abstract

A series of amides of ethacrynic acid was prepared and evaluated for their ability to inhibit Wnt signaling and decrease the survival of CLL cells. Several of the most potent derivatives were active in the low micromolar range. Reduction of the alpha,beta-unsaturated carbon-carbon double bond of EA abrogated both the inhibition of Wnt signaling as well as the decrease in CLL survival. Preliminary mechanism of action studies suggest that these derivatives covalently modify sulfhydryl groups present on transcription factors important for Wnt/beta-catenin signaling.

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