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An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin
- Source :
- Angewandte Chemie (International ed. in English). 56(28)
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Scaffold protein
Tumor spheroid
Antineoplastic Agents
010402 general chemistry
Proteomics
01 natural sciences
Catalysis
03 medical and health sciences
Gene Knockout Techniques
Mice
Cell Line, Tumor
Organometallic Compounds
Animals
Humans
Tumor growth
Cell Proliferation
Chemistry
General Chemistry
Plectin
Neoplasms, Experimental
0104 chemical sciences
030104 developmental biology
Gene Ontology
Biochemistry
Cancer research
Ruthenium Compounds
Drug Screening Assays, Antitumor
Selectivity
Subjects
Details
- ISSN :
- 15213773
- Volume :
- 56
- Issue :
- 28
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie (International ed. in English)
- Accession number :
- edsair.doi.dedup.....718f34f6d1b979cd828a830950da40c3