Optimization of a small molecule probe that restores e-cadherin expression. Issue 19 (1st October 2015)

• Record Type: Journal Article
• Authors: Brogan, John T.; Stoops, Sydney L.; Brady, Suzanne; An, Hanbing; Weaver, Connie; Daniels, J. Scott; Beauchamp, R. Daniel; Lindsley, Craig W.; Waterson, Alex G.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 19(2015)
• Page Start: 4260
• Page End: 4264
• Publication Date: 2015-10-01
• Subjects: E-cadherin -- Structure activity relationship -- Cancer -- Epithelial mesenchymal transition; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.07.104
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: E-cadherin is a ubiquitous trans-membrane protein that has important functions in cellular contacts and has been shown to play a role in the epithelial mesenchymal transition. We have previously reported the use of an HTS screen to identify compounds that are capable of restoring e-cadherin in cancer cells. Here, we report the additional medicinal chemistry optimization of these molecules, resulting in new molecules that restore e-cadherin expression at low micromolar concentrations. Further, we report preliminary pharmacokinetic data on a compound, ML327, that can be used as a probe of e-cadherin restoration.