Optimization of a small molecule probe that restores e-cadherin expression
| Autor: | Alex G. Waterson, Hanbing An, Sydney L. Stoops, J. Scott Daniels, R. Daniel Beauchamp, John T. Brogan, Craig W. Lindsley, Suzanne Brady, Connie Weaver |
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| Rok vydání: | 2015 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Biochemistry Article Mice Structure-Activity Relationship Cell Line Tumor Drug Discovery Molecule Structure–activity relationship Animals Humans Epithelial–mesenchymal transition Molecular Biology Dose-Response Relationship Drug Molecular Structure Chemistry Cadherin Organic Chemistry Isoxazoles Cadherins Small molecule Cell biology Rats Cancer cell Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 25(19) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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