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dc.contributor.authorKwon, S.J.
dc.contributor.authorKim, M.I.
dc.contributor.authorKu, B.
dc.contributor.authorCoulombel, L.
dc.contributor.authorKim, J.H.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorDordick, J.S.
dc.date2010
dc.date.accessioned2022-06-23T04:08:44Z
dc.date.available2022-06-23T04:08:44Z
dc.date.issued2010
dc.identifier.citationUnnatural polyketide analogs selectively target the HER2 signaling pathway in human breast cancer cells, S. J. Kwon, M. I. Kim, B. Ku, L. Coulombel, J.-H. Kim, R.J. Linhardt, and J. S. Dordick, ChemBioChem, 11, 573 – 580, 2010.
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5258
dc.identifier.urihttps://doi.org/10.1002%2Fcbic.200900674
dc.descriptionChemBioChem, 11, 573–580
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractReceptor tyrosine kinases are critical targets for the regulation of cell survival. Cancer patients with abnormal receptor tyrosine kinases (RTK) tend to have more aggressive disease with poor clinical outcomes. As a result, human epidermal growth factor receptor kinases, such as EGFR (HER1), HER2, and HER3, represent important therapeutic targets. Several plant polyphenols including the type III polyketide synthase products (genistein, curcumin, resveratrol, and epigallocatechin-3-galate) possess chemopreventive activity, primarily as a result of RTK inhibition. However, only a small fraction of the polyphenolic structural universe has been evaluated. Along these lines, we have developed an in vitro route to the synthesis and subsequent screening of unnatural polyketide analogs with N-acetylcysteamine (SNAc) starter substrates and malonyl-coenzyme A (CoA) and methylmalonyl-CoA as extender substrates. The resulting polyketide analogs possessed a similar strucutral polyketide backbone (aromatic-2-pyrone) with variable side chains. Screening chalcone synthase (CHS) reaction products against BT-474 cells resulted in identification of several trifluoromethylcinnamoyl-based polyketides that showed strong suppression of the HER2-associated PI3K/AKT signaling pathway, yet did not inhibit the growth of nontransformed MCF-10A breast cells (IC50 > 100 µm). Specifically, 4-trifluoromethylcinnamoyl pyrone (compound 2e) was highly potent (IC50 < 200 nm) among the test compounds toward proliferation of several breast cancer cell lines. This breadth of activity likely stems from the ability of compound 2e to inhibit the phosphorylation of HER1, HER2, and HER3. Therefore, these polyketide analogs might prove to be useful drug candidates for potential breast cancer therapy.
dc.languageen_US
dc.language.isoENG
dc.publisherEuropean Chemical Societies
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleUnnatural polyketide analogs selectively target the HER2 signaling pathway in human breast cancer cells
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.isVersionOfhttps://doi.org/10.1002%2Fcbic.200900674
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)


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