2. Academic Validation
  3. Optimization of a small molecule probe that restores e-cadherin expression

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

  • Bioorg Med Chem Lett. 2015 Oct 1;25(19):4260-4. doi: 10.1016/j.bmcl.2015.07.104.
John T Brogan 1,  Sydney L Stoops 1,  Suzanne Brady 2,  Hanbing An 3,  Connie Weaver 3,  J Scott Daniels 4,  R Daniel Beauchamp 5,  Craig W Lindsley 6,  Alex G Waterson 7
Affiliations

Affiliations

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 2 Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 3 Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 4 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 5 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 6 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 7 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: alex.g.waterson@vanderbilt.edu.
PMID: 26299347 DOI: 10.1016/j.bmcl.2015.07.104
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.

Keywords

Cancer; E-cadherin; Epithelial mesenchymal transition; Structure activity relationship.

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