Metabolite Tales Blog

In Part 1 of this blog on metabolism of small molecules approved by the FDA in 2022 we look at the trends, and whether CYP3A4 still rules.

Andrew Parkinson, Consultant and former Founder and CSO/CEO at Xenotech, debates whether drugs that induce CYP1A enzymes via activation of the AhR receptor should be a cause for concern or not.

In this blog we look at metabolism of covalent drugs, highlighting some interesting stories from the field and metabolism quirks of covalent inhibitors.

The majority of reviews on the application of bioisosteres are focused on effects on potency. In this blog we focus on how bioisosteres can alter metabolism of a drug.

Here we discuss metabolism of drugs in which CYPs catalyse oxidation of tert-butyl groups.

This blog highlights the prospect of exploiting orphan human CYPs for development of targeted anti-cancer agents through a prodrug strategy.

In this blog Consultant and Medicinal Chemistry expert Rob Young explores some of the potential impacts of hydroxyl groups in medicinal chemistry, contextualising opportunities alongside other fundamental structural changes and considering the physical consequences of its introduction.

Steve Djuric, Consultant and ex VP of Medicinal Chemistry at Abbvie, shares his thoughts on the challenges we face today in selecting drug candidates.

In this blog Steve delves into some of the PK demands, including permeability of PROTACs, CYP and AO metabolism, and the impact of AI.

Our guest blogger Guy Webber discusses the reasons for de-risking DMPK and why he advises integrating metabolic de-risking into drug discovery processes.

In this blog we explore the relevance of the mainly extrahepatic epoxygenase CYP2J2. Given it’s role at the crossroads of drug metabolism and endogenous bioactive oxy-lipid synthesis, we discuss whether there is a case for greater importance to be placed on this CYP.

LipMetE is a potentially useful and underutilised efficiency metric that relates logD to microsomal clearance. In this blog post we explore its origins and application to analyse metabolism trends in drug design.

Cyclopropyl groups are an appealing substituent to use in drug design because they impart constraint in aliphatic systems while retaining a high fraction of sp3. Furthermore, the ring strain produces shorter, stronger, more polarised C-H bonds that impart some novel properties, not least the reduced susceptibility to oxidative metabolism by cytochrome P450 (CYP) enzymes. In this blog post we explore the metabolism of various drug structures that contain cyclopropyl groups, revealing that cyclopropyl groups can be used advantageously to diminish oxidative metabolism in some circumstances, but when coupled to amines can lead to potentially reactive intermediates.