When a Neutron Makes the Difference: The Power of Deuterium in Drug Design

Prof. Tracey PIRALI, Department of Pharmaceutical Sciences,
University of Piemonte Orientale, tracey.pirali@uniupo.it

Wednesday 12th November
at 16:30, Sala del Consiglio, building C11
Department of Chemical and Pharmaceutical Sciences

Abstract

Deuterium (D) — the heavy isotope of hydrogen (H) — differs from hydrogen by the presence of a single neutron. It is a rare, stable, non-radioactive, and non-toxic isotope with applications spanning chemistry, biology, and medicine.
Although replacing hydrogen with deuterium represents the smallest possible structural change, this subtle modification can significantly slow down chemical and metabolic reactions, often leading to more stable and longer-lasting therapeutics.
The so-called “deuterium switch” strategy—substituting hydrogen atoms in existing drugs with deuterium—has produced several clinically relevant molecules. A well-known example is deutetrabenazine, approved in 2017 for the treatment of Huntington’s chorea. To date, nearly 20 deuterated drug candidates have reached clinical trials.
While the enthusiasm for the deuterium switch has somewhat declined due to intellectual property challenges, deuterium is now being incorporated earlier in the drug discovery process, enabling the design of entirely new chemical entities. A notable case is deucravacitinib, an allosteric TYK2 inhibitor approved in 2022 for psoriasis.

Tracey Pirali is a full professor of Medicinal Chemistry at the University of Piemonte Orientale. She earned her degree in Pharmaceutical Chemistry and Technology (CTF) in
2004 and completed her PhD in the laboratory of Prof. Tron in 2008. As a visiting scientist, she worked with Prof. Zhu (Paris, CNRS) and Prof. Greaney (Edinburgh, School of
Chemistry). In 2013, she established her own research group in Novara, at the University of Piemonte Orientale. Her research includes exploring the soft drug concept in topical delivery, using deuterium to enhance the pharmacokinetic profiles of bioactive molecules, employing PROTAC technology for protein degradation modulation, and advancing multicomponent reactions to accelerate synthesis. These approaches target various therapeutic areas, such as cancer immunotherapy and neuropathic pain. In 2012, Prof. Pirali was awarded the Farmindustria Prize by the Italian Chemical Society. In 2019 she co-founded ChemICare, a spin-off company dedicated to developing  calcium channel modulators for treating Duchenne muscular dystrophy. Since 2019, she has served as the Director of the Erasmus Mundus Joint Master EMOTION funded by the European Union. She is a member of the Board of the Medicinal Chemistry Division, Italian Chemical Society.