Small molecule drug metabolite synthesis and identification : why, when and how?
In this open access review in Drug Discovery Today we look at why, when and how metabolites of small-molecule drugs are synthesised from the perspective of a specialist CRO.
“Congratulations on publishing this keynote review that delves into the critical role of metabolites in discovery and development. Your review provides a valuable deep dive into the reasons for metabolite synthesis, the timing, and the methods used for their identification. It also highlights the impact of regulatory frameworks, emphasizes the importance of understanding metabolite profiles, and underscores the need for early assessment of metabolites for potential drug-drug interactions, all based on compelling case studies.”
Dr Thomas Fuchß, Merck KGaA
Abstract
The drug discovery and development process encompasses the interrogation of metabolites arising from the biotransformation of drugs. Here we look at why, when and how metabolites of small-molecule drugs are synthesised from the perspective of a specialist contract research organisation, with particular attention paid to projects for which regulatory oversight is relevant during this journey. To illustrate important aspects, we look at recent case studies, trends and learnings from our experience of making and identifying metabolites over the past ten years, along with with selected examples from the literature.
Highlights
- Commentary on when and how drug metabolite synthesis fits into the overall drug development pathway and the influence of regulatory guidelines.
- The tool box of techniques used by a specialist contract research organisation to make phase I and II metabolites.
- Case studies illustrating recent examples, including the significance of selected drug metabolites and their synthesis.
Paper (open access)
Shanu-Wilson J, Coe S, Evans L, Steele J, Wrigley S. Small molecule drug metabolite synthesis and identification: why, when and how? Drug Discov Today. 2024 Mar 5;29(5):103943. doi: 10.1016/j.drudis.2024.103943. Epub ahead of print. PMID: 38452922.