title: Amide derivatives of ethacrynic acid: synthesis and evaluation as antagonists of Wnt/beta-catenin signaling and CLL cell survival.
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.
authors.affiliation: Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093-0820, USA.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Jin
authors.forename: Desheng
authors.initials: D
authors.lastname: Lu
authors.forename: Shiyin
authors.initials: S
authors.lastname: Yao
authors.forename: Christina C N
authors.initials: CC
authors.lastname: Wu
authors.forename: Jerry X
authors.initials: JX
authors.lastname: Liu
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Carson
authors.forename: Howard B
authors.initials: HB
authors.lastname: Cottam
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004976:Ethacrynic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051153:Wnt Proteins; D051176:beta Catenin; D002244:Carbon; D004976:Ethacrynic Acid