Biotransformation and bioactivation reactions – 2017 literature highlights^**

Abstract

This annual review is the third one to highlight recent advances in the study and assessment of biotransformations and bioactivations (Table 1). We followed the same format as the previous years with selection and authoring each section (see Baillie et al. 2016; Khojasteh et al. 2017). We acknowledge that many universities no longer train students in mechanistic biotransformation studies reflecting a decline in the investment for those efforts by public funded granting institutions. We hope this work serves as a resource to appreciate the knowledge gained each year to understand and hopefully anticipate toxicological outcomes dependent on biotransformations and bioactivations.

This effort itself also continues to evolve. I am pleased that Drs. Rietjens and Miller have again contributed to this annual review. We would like to welcome Kaushik Mitra as an author for this year’s issue, and we thank Deepak Dalvie for his contributions to last year’s edition. We have intentionally maintained a balance of authors such that two come from an academic setting and two come from industry. As always, please drop us a note if you find this review helpful. We would be pleased to hear your opinions of our commentary, and we extend an invitation to anyone who would like to contribute to a future edition of this review.

Additional information

Notes on contributors

S. Cyrus Khojasteh

S. Cyrus Khojasteh, heads the Biotransformation Function at Genentech (South San Francisco). His research focuses on the mechanisms of biotransformation in drug discovery and development, with a particular interest in mechanisms of biotransformation as they relate to small molecules and a growing focus on macrocyclic peptides and drug payloads of antibody drug conjugates. Cyrus received his B.S. from the University of California at Berkeley and his Ph.D. in Medicinal Chemistry from the University of Washington under the direction of Dr Sidney D. Nelson.

Grover P. Miller

Grover P. Miller, is a full Professor in the Department of Biochemistry and Molecular Biology with a joint appointment in Biomedical Informatics at the University of Arkansas for Medical Sciences. He received BS degrees in Biochemistry and Chemistry with minors in English and French from the Louisiana State University. He obtained his PhD in Chemistry mentored by Stephen J. Benkovic at the Pennsylvania State University and subsequent postdoctoral training as an NIH NRSA fellow mentored by F. Peter Guengerich at Vanderbilt University. His research spans experimental and computational approaches to assess metabolic activation and detoxification of drugs, pollutants, and dietary compounds from the perspective of a chemist.

Kaushik Mitra

Kaushik Mitra, heads the Molecular and Investigative Toxicology group within the Department of Safety Assessment at Merck. He transitioned to this function in 2016 following a career for 13 years in the Department of Pharmacodynamics, Pharmacokinetics and Drug Metabolism where he held leadership roles in biotransformation and ADME groups. His research interests focus on mechanisms of drug-induced adverse effects such as liver injury and genetic toxicity. Kaushik received his Ph.D. in Organic Chemistry from the University of Missouri, Columbia and subsequent post-doctoral training in Biological Engineering from the Massachusetts Institute of Technology.

Ivonne M. C. M. Rietjens

Ivonne M. C. M. Rietjens, is full professor and head of the division of Toxicology at Wageningen University, The Netherlands. She is a member of the Royal Netherlands Academy of Arts and Sciences (KNAW), and chair or vice chair of many national and international advisory committees in the field of risk assessment. Her research focuses on the risk evaluation of food borne natural toxins with an emphasis on the role of reactive intermediates and DNA adduct formation, physiologically based kinetic (PBK) models for bioactivation and detoxification, genetic polymorphisms and consequences of life style factors for individual sensitivity and risk assessment and alternatives for animal testing.