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Introduction to ADMET: solving problems chemically

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On 23 October 2008, SCI’s Young Chemists' Panel held its popular 'Introduction to ADMET: solving problems chemically' meeting at SCI headquarters in Belgravia, London. This event, the third in the series, aims to highlight the challenges associated with ADMET (absorption, distribution, metabolism, elimination and toxicity) in medicinal chemistry. The three speakers, Peter Astles, Darren McKerrecher and Ted Parton, have a combined total of 50 years experience with a range of well-known pharmaceutical companies.

The aim of the day was to provide participants with a practical understanding of how to diagnose common ADMET problems, and how these problems may be overcome chemically using recent examples from drug discovery programmes. Topics discussed included solubility, polar surface area, P-gp efflux, clearance, cytochrome P450s and drug-drug interactions, and hERG.

Historically, drug discovery programmes have been guided almost exclusively by SAR, to maximise interaction with a therapeutic target. However, designing drugs is not just about optimising potency. The goal of ADMET-guided synthesis is to maximise the ability of a possible drug to access therapeutic target in vivo. Of all the attributes that determine a drug’s ultimate in vivo efficacy, physicochemical properties are paramount and deserve considerable scrutiny by the drug discovery team. Moreover, as solubility, pKa, and lipophilicity are so integrally linked with chemical structure, these properties in some respects can be manipulated by chemical modifications. Knowledge of ADMET issues can help to design better drugs and lead to fewer failures in development.

Gwen Eyre (Sygnature CSL) and Rebekah Beevers (Domainex Ltd)
Young Chemists’ Panel

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