Advances in the study of drug metabolism – symposium report of the 12th Meeting of the International Society for the Study of Xenobiotics (ISSX)

Abstract

The 12th International Society for the Study of Xenobiotics (ISSX) meeting, held in Portland, OR, USA from July 28 to 31, 2019, was attended by diverse members of the pharmaceutical sciences community. The ISSX New Investigators Group provides learning and professional growth opportunities for student and early career members of ISSX. To share meeting content with those who were unable to attend, the ISSX New Investigators herein elected to highlight the “Advances in the Study of Drug Metabolism” symposium, as it engaged attendees with diverse backgrounds. This session covered a wide range of current topics in drug metabolism research including predicting sites and routes of metabolism, metabolite identification, ligand docking, and medicinal and natural products chemistry, and highlighted approaches complemented by computational modeling. In silico tools have been increasingly applied in both academic and industrial settings, alongside traditional and evolving in vitro techniques, to strengthen and streamline pharmaceutical research. Approaches such as quantum mechanics simulations facilitate understanding of reaction energetics toward prediction of routes and sites of drug metabolism. Furthermore, in tandem with crystallographic and orthogonal wet lab techniques for structural validation of drug metabolizing enzymes, in silico models can aid understanding of substrate recognition by particular enzymes, identify metabolic soft spots and predict toxic metabolites for improved molecular design. Of note, integration of chemical synthesis and biosynthesis using natural products remains an important approach for identifying new chemical scaffolds in drug discovery. These subjects, compiled by the symposium organizers, presenters, and the ISSX New Investigators Group, are discussed in this review.

Keywords:

• Biosynthetic lead diversification
• CYP1A1
• cytochrome P450
• drug metabolism
• matched molecular pairs
• molecular docking
• predictive tools
• site of metabolism
• X-ray crystallography

Acknowledgments

The authors thank the International Society for the Study of Xenobiotics, especially Zoë Fuller and Anne Prendergast, for their unwavering support in the development of this manuscript.

Disclosure statement

The authors declare no conflict of interest. The content of this publication is solely the responsibilities of the authors and do not necessarily represent the official views of NIH. The research work conducted in this publication is not affiliated with Gilead Sciences.

Additional information

Funding

The work of Emily E. Scott and Aaron G. Bart was supported by National Institutes of Health Grants R37 GM076343 (to EES). Mary Alexandra Schleiff was supported by NIH training grant T32GM106999. Jasleen K. Sodhi was supported in part by an American Foundation for Pharmaceutical Education Predoctoral Fellowship, NIGMS grant R25 GM56847 and a Louis Zeh Fellowship.