a chemocentric approach to the identification of cancer targets一个chemocentric癌症目标的识别方法.pdfVIP

A Chemocentric Approach to the Identification of Cancer Targets ´ 1 ¨ 1 2 2 3 3 Beata Flachner , Zsolt Lorincz , Angelo Carotti , Orazio Nicolotti , Praveena Kuchipudi , Nikita Remez , 3 ´ ´ ´ 4 ´ ´ 5 ´ ´ 5 ´ 1 3 Ferran Sanz , Jozsef Tovari , Miklos J. Szabo , Bela Bertok , Sandor Cseh , Jordi Mestres *, ¨ ´ 1* Gyorgy Dorman 1TargetEx, Dunakeszi, Hungary, 2 Medicinal Chemistry Department, University of Bari ‘‘Aldo Moro’’, Bari, Italy, 3 IMIM – Hospital del Mar Research Institute and Universitat Pompeu Fabra, Barcelona, Catalonia, Spain, 4 National Institute of Oncology, Budapest, Hungary, 5 AMRI Hungary Zrt., Budapest, Hungary Abstract A novel chemocentric approach to identifying cancer-relevant targets is introduced. Starting with a large chemical collection, the strategy uses the list of small molecule hits arising from a differential cytotoxicity screening on tumor HCT116 and normal MRC-5 cell lines to identify proteins associated with cancer emerging from a differential virtual target profiling of the most selective compounds detected in both cell lines. It is shown that this smart combination of differential in vitro and in silico screenings (DIVISS) is capable of detecting a list of proteins that are already well accepted cancer drug targets, while complementing it with additional proteins that, targeted selectively or in combination with others, could lead to synergistic benefits for cancer therapeutics. The complete list of 115 proteins identified as being hit uniquely by compounds showing selective antiproliferative effe