Drug Discovery Today  Volume 00, Number 00  November 2013 REVIEWS Teaser Drug discovery and development suffers from high cost and attrition owing to toxicity. The application of unique toxicogenomic platforms has the potential to produce safer drugs and decrease research and development costs. Current status and future prospects of toxicogenomics in drug discovery Saifur R. Khan 1 , Argishti Baghdasarian 1 , Richard P. Fahlman 2 , Karim Michail 1,3 and Arno G. Siraki 1 1 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada 2 Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada 3 Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt In drug discovery and development (DDD), the efficacy, safety and cost of new chemical entities are the main concerns of the pharmaceutical industry. Continuously updated and stricter recommendations imposed by regulatory authorities result in greater challenges being faced by the industry. Reliable high-throughput techniques integrated with well- designed analytical tools at all stages of DDD (termed ‘next-generation DDD’) could be a possible approach to obtaining new drug approval by cutting costs as well as ensuring the highest level of patient safety. In this review, we describe the various components of holistic toxicogenomics with examples of applications, and discuss the various analytical tools and platforms to illustrate the current status and prospects of next-generation DDD. DDD, currently one of the most challenging and costly businesses, begins with the identification of new drug candidates either by systematic screening or serendipity, and generally ends after the compound has successfully passed clinical trials. Typically, 90% or more of the budget is spent on clinical trials, mainly in Phase III (http://www.manhattan-institute.org/html/fda_05.htm). One of the most common causes of Phase III failure is drug-induced toxicity. Additionally, drug withdrawals from the market also contribute to the escalation of costs of DDD, with subsequent drops in new lead discoveries. In a study of 548 new lead compounds approved between 1975 and 1999, 56 acquired a black box warning (the strongest warning by the FDA for a scientifically proved significant risk of serious or even life threatening adverse effects) and 16 were withdrawn [1]. A report by the North Carolina General Assembly (NCGA) (29 March, 2012 meeting; subcommittee on pharmaceuticals liability) described how the US Food and Drug Administration (FDA) had approved approximately 300 new drug applications over the past decade, of which at least 15 have since been withdrawn from the US market (http://www.ncleg.net). Surveys indicate that, in the USA, a new lead compound takes 10–15 years on average to reach the market, with an associated cost of approximately US$1.8 billion and an average success rate of only 8% [2]. Increasing the success rate of DDD and decreasing drug attrition, although challenging, could Reviews  KEYNOTE REVIEW Saifur R. Khan is pursuing his PhD at the University of Alberta, which awarded him a doctoral recruitment scholarship. He is investigating the immune- modulatory role of antitu- berculosis drugs by using multiple platforms, including omics. He has been awarded the Bill Bridger Award of Excellence for highest achievement among all Alberta Innovate Graduate Student Scholarship holders in 2012. He obtained his MSc in Biotechnology from Brac University (Bangladesh) in 2008, receiving the Vice-Chancellor Medal, and a B.Pharm (Hons) in 2005 from the University of Dhaka (Bangladesh). He worked in research and development at Incepta Pharmaceuticals Ltd, Bangladesh, from 2006 to 2011. Richard P. Fahlman is an associate professor in the Department of Bio- chemistry and an adjunct associate professor in the Department of Oncology in the Faculty of Medicine and Dentistry at the University of Alberta. In addition to Faculty appointments, he is also the associate director for the Institute for Biomole- cular Design, the mass spectrometry and analytical core facility at the University of Alberta. He has a PhD in Biochemistry and Molecular Biology (2001) from Simon Fraser University. Arno G. Siraki is an assistant professor in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta. His graduate studies were car- ried out in the Leslie Dan Faculty of Pharmacy at the University of Toronto and involved mechanistic stu- dies of drug- and xenobiotic-catalyzed oxidative stress and the application of structure–activity relationships. His postdoctoral studies at the National Institute of Environmental Health Sciences focused on associating the formation of drug free radical metabolites with protein radicals. Siraki’s current interests are in determining the role of drug free radical metabolites in adverse drug reactions. Corresponding author:. Siraki, A.G. (siraki@ualberta.ca) 1359-6446/06/$ - see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.drudis.2013.11.001 www.drugdiscoverytoday.com 1