Research Paper: CarcinogenesisThe protein kinase promiscuities in the cancer-preventive mechanisms of NSAIDsNorvaisas, Povilas; Chan, Diana; Yokoi, Kenji; Dave, Bhuvanesh; Ziemys, ArturasAuthor Information The Houston Methodist Research Institute, Houston, Texas, USA Present address: Povilas Norvaisas: Institute of Biotechnology, Vilnius University, Vilnius 02241, Lithuania. All supplementary digital content is available directly from the corresponding author. Correspondence to Arturas Ziemys, PhD, The Houston Methodist Research Institute, Houston, TX 77030, USA Tel: +1 713 441 7320; fax: +1 713 441 7438; e-mail: [email protected] Received August 16, 2014 Accepted December 23, 2014 European Journal of Cancer Prevention: January 2016 - Volume 25 - Issue 1 - p 77-84 doi: 10.1097/CEJ.0000000000000129 Buy Metrics Abstract NSAIDs have been observed to have cancer-preventive properties, but the actual mechanism is elusive. We hypothesize that NSAIDs might have an effect through common pathways and targets of anticancer drugs by exploiting promiscuities of anticancer drug targets. Here, we have explored NSAIDs by their structural and pharmacophoric similarities with small anticancer molecules. In-silico analyses have shown a strong similarity between NSAIDs and protein kinase (PK) inhibitors. The calculated affinities of NSAIDs were found to be lower than the affinities of anticancer drugs, but higher than the affinities of compounds that are not specific to PKs. The competitive inhibition model suggests that PK might be inhibited by around 10%, which was confirmed by biochemical screening of some NSAIDs against PKs. NSAIDs did not affect all PKs universally, but had specificities for certain sets of PKs, which differed according to the NSAID. The study revealed potentially new features and mechanisms of NSAIDs that are useful in explaining their role in cancer prevention, which might lead to clinically significant breakthroughs in the future. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.