Optimization of a small molecule probe that restores e-cadherin expression.

Brogan JT, Stoops SL, Brady S, An H, Weaver C, Daniels JS, Beauchamp RD, Lindsley CW, Waterson AG
Bioorg Med Chem Lett. 2015 25 (19): 4260-4

PMID: 26299347 · PMCID: PMC4567403 · DOI:10.1016/j.bmcl.2015.07.104

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.

Copyright © 2015 Elsevier Ltd. All rights reserved.

MeSH Terms (10)

Animals Cadherins Cell Line, Tumor Dose-Response Relationship, Drug Humans Isoxazoles Mice Molecular Structure Rats Structure-Activity Relationship

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