| Literature DB >> 28547791 |
Samuel M Meier1,2, Dominique Kreutz1, Lilli Winter3, Matthias H M Klose2,4, Klaudia Cseh4, Tamara Weiss5, Andrea Bileck1, Beatrix Alte6, Johanna C Mader1, Samir Jana7, Annesha Chatterjee7, Arindam Bhattacharyya7, Michaela Hejl4, Michael A Jakupec2,4, Petra Heffeter2,6, Walter Berger2,6, Christian G Hartinger8, Bernhard K Keppler2,4, Gerhard Wiche3, Christopher Gerner1.
Abstract
Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model.Entities:
Keywords: anticancer agents; plectin; proteomics; ruthenium; target identification
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Year: 2017 PMID： 28547791 DOI： 10.1002/anie.201702242
Source DB: PubMed Journal: Angew Chem Int Ed Engl ISSN： 1433-7851 Impact factor: 15.336