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An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin
Author(s) -
Meier Samuel M.,
Kreutz Dominique,
Winter Lilli,
Klose Matthias H. M.,
Cseh Klaudia,
Weiss Tamara,
Bileck Andrea,
Alte Beatrix,
Mader Johanna C.,
Jana Samir,
Chatterjee Annesha,
Bhattacharyya Arindam,
Hejl Michaela,
Jakupec Michael A.,
Heffeter Petra,
Berger Walter,
Hartinger Christian G.,
Keppler Bernhard K.,
Wiche Gerhard,
Gerner Christopher
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201702242
Subject(s) - plectin , chemistry , cancer research , in vitro , selectivity , computational biology , microbiology and biotechnology , biology , cytoskeleton , biochemistry , cell , intermediate filament , catalysis
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.