Author:
Huang Yi,Furuno Masaaki,Arakawa Takahiro,Takizawa Satoshi,de Hoon Michiel,Suzuki Harukazu,Arner Erik
Abstract
AbstractOwing to safety concerns or insufficient efficacy, few drug candidates are approved for marketing. Drugs already on the market may be withdrawn due to adverse effects (AEs) discovered after market introduction. Comprehensively investigating the on-/off-target effects of drugs can help expose AEs during the drug development process. We have developed an integrative framework for systematic identification of on-/off-target pathways and elucidation of the underlying regulatory mechanisms, by combining promoter expression profiling after drug treatment with gene perturbation of the primary drug target. Expression profiles from statin-treated cells and HMG-CoA reductase knockdowns were analyzed using the framework, allowing for identification of not only reported adverse effects but also novel candidates of off-target effects from statin treatment, including key regulatory elements of on- and off-targets. Our findings may provide new insights for finding new usages or potential side effects of drug treatment.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Publisher
Springer Science and Business Media LLC
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