Archived Content

Cambridge Healthtech Institute’s Inaugural
Physicochemical Property Analysis
Improving the Drug Discovery Process by Optimizing Physical Properties
April 18-19 

Day 1 | Day 2
Download Drug Discovery Chemistry Brochure or Physicochemical Brochure 

The optimization of physical properties of a compound is fundamental to the drug discovery process, mainly due to their influence on absorption and distribution in vivo. This provides insight into the in vivo transport processes and knowing the properties will help with choosing the optimal compounds for the task. It saves costs and time when compounds are being properly analyzed in the design stage before they are moving into development, as it is important to consider questions such as how hydrophobicity will affect the solubility of a drug down the line or how the charge of the compound interacts with the absorption by a transport mechanism. Also, the use of predictive models is important, but again, without consideration of the actual physical chemical property of the new compound, the analyses will be based on a different set of data. This meeting will discuss what it takes to create selective and efficacious compounds and to understand the biological data by analyzing the physicochemical properties early on.


12:30 pm Registration

1:30 Chairperson’s Opening Remarks



1:40 Getting Physical in Drug Discovery; Where Next for Property Profiling and Predictive Methods?

Robert J. Young, Ph.D., GlaxoSmithKline

A growing body of evidence indicates that much of the attrition in drug discovery can be attributed to the sub-optimal physical properties of experimental molecules, especially in pre-clinical activities. Molecules that are overly lipophilic and/or highly aromatic have been shown to posses greatly increased risk in studies to assess developability and promiscuity profiles; with impact over and above the inherent correlation between logP and #Ar rings. This led to the so-called property forecast indices, (PFI = log P or log DpH7.4 + #Ar), simplistic yet powerful predictors of risk; these are enhanced by the utilisation of improved lipophilicity measures and estimates based on chromatographic methods. Data illustrating these principles will be discussed, posing questions for future predictive methods. Successful molecules can be further discriminated when PFI is taken together with ligand efficiency measures, pointing to a useful indicator of likely success in drug discovery.

2:55 Getting Physical in Drug Discovery: A Suite of Physicochemical Methods to Enable Successful Drug Discovery

Alan P. Hill, Ph.D., Team Leder, PhysChem, Department of Analytical Chemistry, GlaxoSmithKline, Stevenage UK

Physicochemical measurements are key enablers for successful medicinal chemistry. However to maximise the likelihood of a success, it is essential that assays offered provide data that is appropriate to the stage of the project and additionally have sufficient capacity to meet demands. The presentation will provide an overview of a cohesive approach to physicochemical measurement (as applied within GSK) that effectively guides medicinal chemistry projects to produce robust candidate molecules with optimal physicochemical properties.

3:10 Modulating Physicochemical Properties to Improve ADME Outcomes

Jan Wahlstrom, Ph.D., Principal Scientist, Amgen

Alterations of physicochemical properties such as molecular weight, log d, polar surface area or pKa may influence the absorption, distribution, metabolism or excretion (ADME) of a chemical series in a chemotype-dependent manner. Application of mechanistic approaches to solving ADME issues provides insight as to why a change in properties causes a desired outcome in some cases, while leading to poorer outcomes in others. This seminar will focus on case studies outlining common ADME issues faced during the drug discovery process and the approaches used to resolve them.

3:40 Networking Refreshment Break in Exhibit Hall with Poster Viewing 

4:20 Practical Concepts in Fragment-Based Drug Ddiscovery

Marcel Verdonk, Ph.D., Director, Computational Chemistry and Informatics, Astex Therapeutics, Inc.



4:50 The Intricacies of Interpreting Pharmaceutical Data

Terry Stouch, Ph.D., President, R&D, Science for Solutions, LLC

Pharmaceutical research data that is extremely valuable within context could be worthless outside of that context or when lumped with other data. We will discuss these issues supported by many practical examples from several pharmaceutical companies, commercial and open source databases, and the literature. Diverse types of pharmaceutical data will be discussed including physicochemical properties such as solubility, logP, logD, Caco-2, and pKa. The vital meta data, its importance in the proper use of the data, the mistakes and problems that arise from ignoring it, and the reasons it is often ignored, will be outlined. Recommendations that will ameliorate these problems and enhance data use and value will be offered for better data capture and data basing and for holistic data presentation that will aid interpretation.

5:20 Interactive Breakout Discussions

In this interactive session, several topics will be offered for discussions and delegates are invited to choose a breakout topic of interest and join the moderated discussion at hand. In this informal setting, participants are encouraged to share examples from their work, vet ideas with peers and be part of a group problem-solving endeavor. We emphasize that this discussion is an informal exchange amongst scientists and is not meant to be, in any way, a product discussion.

Topic 1: Challenges of Thermodynamic Analysis

Moderator: Ernesto Freire, Ph.D., Henry Walters Professor, Johns Hopkins University

Topic 2: Hydrophobicity in Drug Discovery:  Measurement or Calculation: Which Moves Drug Discovery Forward?

Moderator: Alan P. Hill, Ph.D., Team Leder, PhysChem, Department of Analytical Chemistry, GlaxoSmithKline, Stevenage UK

  • When is hydrophobicity important?
  • Is calculation good enough?
  • logP or LogD?

6:30 End of Day

Day 1 | Day 2
Download Drug Discovery Chemistry Brochure or Physicochemical Brochure