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. 2017 Jul 3;56(28):8267-8271.
doi: 10.1002/anie.201702242. Epub 2017 May 26.

An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin

Samuel M Meier  1   2 , Dominique Kreutz  1 , Lilli Winter  3 , Matthias H M Klose  2   4 , Klaudia Cseh  4 , Tamara Weiss  5 , Andrea Bileck  1 , Beatrix Alte  6 , Johanna C Mader  1 , Samir Jana  7 , Annesha Chatterjee  7 , Arindam Bhattacharyya  7 , Michaela Hejl  4 , Michael A Jakupec  2   4 , Petra Heffeter  2   6 , Walter Berger  2   6 , Christian G Hartinger  8 , Bernhard K Keppler  2   4 , Gerhard Wiche  3 , Christopher Gerner  1
Affiliations

An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin

Samuel M Meier et al. Angew Chem Int Ed Engl. .

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.

Keywords: anticancer agents; plectin; proteomics; ruthenium; target identification.

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