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We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays. The drug ethoxzolamide and the natural compound piperlongumine, present in Piper longum L, showed hMAO-B activity with IC<jats:sub>50<\/jats:sub>values of 25 and 65\u2009\u03bcM respectively. Five candidates, including lapatinib, SB-202190, RO-316233, GW786460X and indirubin-3\u2032-monoxime were tested against human COX-1. Compounds SB-202190 and RO-316233 showed a IC<jats:sub>50<\/jats:sub>in hCOX-1 of 24 and 25\u2009<jats:italic>\u03bc<\/jats:italic>M respectively (similar range as potent inhibitors such as diclofenac and indomethacin in the same experimental conditions). Lapatinib and indirubin-3\u2032-monoxime showed moderate hCOX-1 activity (19.5% and 28% of enzyme inhibition at 25\u2009\u03bcM respectively). Our modeling constitutes a multi-target predictor for large scale virtual screening with potential in lead discovery, repositioning and drug safety.<\/jats:p>","DOI":"10.1038\/srep36969","type":"journal-article","created":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T11:26:40Z","timestamp":1479209200000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Computational Drug Target Screening through Protein Interaction Profiles"],"prefix":"10.1038","volume":"6","author":[{"given":"Santiago","family":"Vilar","sequence":"first","affiliation":[]},{"given":"El\u00edas","family":"Quezada","sequence":"additional","affiliation":[]},{"given":"Eugenio","family":"Uriarte","sequence":"additional","affiliation":[]},{"given":"Stefano","family":"Costanzi","sequence":"additional","affiliation":[]},{"given":"Fernanda","family":"Borges","sequence":"additional","affiliation":[]},{"given":"Dolores","family":"Vi\u00f1a","sequence":"additional","affiliation":[]},{"given":"George","family":"Hripcsak","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,11,15]]},"reference":[{"key":"BFsrep36969_CR1","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/nrd3478","volume":"10","author":"M Rask-Andersen","year":"2011","unstructured":"Rask-Andersen, M., Almen, M. 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