Dozens of presumed inactive ingredients may impact human biology

Research from the UCSF School of Pharmacy and the Novartis Institutes for BioMedical Research (NIBR) has recently found that several common excipients—inactive ingredients in drugs, like dyes and preservatives—may interact with human proteins in ways that produce unintended side effects.

The team, led by UCSF’s Brian Shoichet, PhD, and NIBR’s Laszlo Urban, PhD, used computational methods to sift through a database of thousands of excipients, seeking to identify those that were likely to bind to human proteins. They found 38 of these supposedly benign compounds that may have an undesired impact on human health.

The groups of UCSF’s Kathy Giacomini, PhD, as well as the University of North Carolina at Chapel Hill’s Bryan Roth, PhD, then validated some of these predicted interactions in the laboratory.

Shoichet is a faculty member in the School’s Department of Pharmaceutical Chemistry. Giacomini is a faculty member in the Department of Bioengineering and Therapeutic Sciences, a joint department of the UCSF Schools of Pharmacy and Medicine, as well as the co-director of the FDA-funded UCSF-Stanford Center of Excellence in Regulatory Science and Innovation (CERSI), which provided additional support for the project.

“These data illustrate that while many excipient molecules are in fact inert, a good number may have previously unappreciated effects on human proteins known to play an important role in health and disease,” Shoichet told UCSF News. “We demonstrate an approach by which drug makers could in the future evaluate the excipients used in their formulations, and replace biologically active compounds with equivalent molecules that are truly inactive.”


Some ‘inert’ drug ingredients may be biologically active (UCSF News)

The activities of drug inactive ingredients on biological targets (Science)

About the School: The UCSF School of Pharmacy is a premier graduate-level academic organization dedicated to improving health through precise therapeutics. It succeeds through innovative research, by educating PharmD health professional and PhD science students, and by caring for the therapeutics needs of patients while exploring innovative new models of patient care. The School was founded in 1872 as the first pharmacy school in the American West. It is an integral part of UC San Francisco, a leading university dedicated to promoting health worldwide.