Expertise
"An expert is someone who knows some of the worst mistakes that can be made in his subject, and how to avoid them"
- Werner Heisenberg
"An expert is someone who has made all the mistakes which can be made, in a narrow field"
- Niels Bohr
The Medicinal Chemistry and DMPK/ADME disciplines are critical for the progression of drug discovery and development projects.
We have a combined 50 years of experience in drug discovery both from a medicinal chemistry and especially DMPK/ADME perspective. Mostly focused on small molecules and bRo5 space, we have also worked in biologics and ADCs. In addition, our experience includes input to multiple projects that have successfully progressed to clinical trials and ultimately NDA submission.
"I thought all molecules were small...?" - Callum (Kevin's son-in-law)
Explore our areas of expertise:
Preclinical DMPK
In drug discovery, optimisation of chemical equity from an ADME pharmacokinetic perspective is critical in selection of high-quality development candidates. Balancing physiochemical properties to achieve suitable absorption, distribution to the site of action and half-life (alongside potency and selectivity/safety) for the desired target product profile are essential in any drug discovery project. We have extensive experience in driving medicinal chemistry strategies to optimise for improved pharmacokinetic profiles and interpreting and assessing ADME and DMPK data. We work with drug discovery teams to ensure the right ADME and DMPK experiments are run, analysis is robust and full value from the experiments is extracted, and that MedChem/DMPK/ADME strategies are addressing key questions to efficiently move towards high-quality development candidates.
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Stepan, A.; Mascitti, V.; Beaumont, K.; Kalgutkar, A. Metabolism-guided drug design. MedChemComm (2013), 4(4), 631-652.
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Smith, D. A., Beaumont, K., Maurer, T. and Di, L. Volume of Distribution in Drug Design. Journal of Medicinal Chemistry, Journal of Medicinal Chemistry (2015), 58(15), 5691-5698.
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Smith, Dennis A.; Beaumont, Kevin; Maurer, Tristan S.; Di, Li. Relevance of Half-Life in Drug Design. Journal of Medicinal Chemistry (2017), 61(10), 4273–4282.
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Smith, Dennis A.; Beaumont, Kevin; Maurer, Tristan S.; Di, Li. Clearance in Drug Design. Journal of Medicinal Chemistry (2019), 62(5), 2245-2255.
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Dennis Smith, Kevin Beaumont, Tristan S. Maurer, Li Di. Insights on Volume of Distribution of Acids. Journal of Medicinal Chemistry (2025), 68 (16), 16901–16911.
Free Drug Principles
"Live Free Or Die" - New Hampshire state motto
The Free Drug Hypothesis is an elegant and simple (but sometimes counterintuitive) description of how drugs behave, and how non-specific binding impacts the pharmacokinetics and pharmacodynamics relationship of a compound. Proper implementation of the Free Drug Hypothesis helps to rationalise drug discovery data and accelerate projects. It can change SAR interpretation (especially for highly bound compounds) and can help with improved in vitro-in vivo correlation (IVIVc) to rationally optimise series. We can educate on the Free Drug Hypothesis, advise on proper implementation and data analysis in drug discovery projects and help to develop strategies for optimisation of compounds using free drug principles.
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Peter J H Webborn, Kevin Beaumont, Iain J Martin, Dennis A Smith. Free Drug Concepts: A Lingering Problem in Drug Discovery. Journal of Medicinal Chemistry (2025), 68 (7), 6850-6856.
Human PK and Dose-to-Man Prediction
"Prediction is difficult, especially about the future" - Niels Bohr
Prediction of human PK and dose has become an important part of preclinical drug discovery – leading to reduced attrition due to poor PK in clinical trials and acceleration of drug discovery projects by providing clinically-relevant context to Lead Optimisation campaigns. Benchmarking early on in a drug discovery campaign can help to guide compound design and optimisation towards a target product profile, through identifying the key parameters for reduced dose requirements. With many years of experience, we understand the requirements, pitfalls and uncertainties in human PK prediction, allowing for timely and impactful analysis for projects. We can present principles and case studies of human PK prediction, inform on data requirements for prediction, run human PK and dose calculations and advise on the interpretation of results.
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Maurer, Tristan S.; Smith, Dennis A.; Beaumont, Kevin; Di, Li. Dose Predictions for Drug Design. Journal of Medicinal Chemistry (2020), 63(12), 6423-6435.
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Harrison, A.; Gardner, I.; Hay, T.; Dickins, M.; Beaumont, K.; Phipps, A.; Purkins, L.; Allan, G.; Christian, R.; Duckworth, J. Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms. Xenobiotica (2012), 42(1), 57-74.
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Beaumont, K.; Gardner, I.; Chapman, K; Hall, M.; Rowland, M. Toward an integrated human clearance prediction strategy that minimizes animal use. Journal of Pharmaceutical Sciences (2011), 100 (10), 4518-4535.
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Beaumont, Kevin; Smith, Dennis A., Does human pharmacokinetic prediction add significant value to compound selection in drug discovery research? Current Opinion in Drug Discovery & Development (2009), 12(1), 61-71.
Clinical Development
Post-candidate selection, the DMPK discipline is important in supporting the design of safety studies and providing the ADME/DMPK story of the candidate for IND/CTA submission in support of Phase I studies. Finally, for candidate drugs progressing through Phase II/III studies, it is important to define the DMPK strategy that will support the full NDA regulatory submission for licencing of the drug. Having supported over 150 candidates into first-in-human studies, we are highly experienced in formulating IND to NDA strategies and preparing regulatory submissions. We can provide insight, guidance and support to your project into and throughout clinical trials.