Lipophilic and fate in dev

The first of these two papers, examining the physical chemical properties of drugs and the in-vivo and clinical outcomes, caused a stir when first published. This resulted in the one of the authors going ‘on tour’, around the conference circuit, for about a year, as we recall. A simple study comparing the properties of successful phase 1,2 and 3 drugs, against those that were discontinued produced a simple conclusion. Other properties were also examined and the authors subsequently produced more detailed studies that were subsequently only disclosed at conferences. The work led, we believe to the term ‘developability’, and various methods of calculating a score.

The second paper performs a more rigorous statistical study of compound properties and in-vivo outcomes. This work is quite detailed, and quite hard to follow the stats, but importantly the work considers the inter-connectivity of properties.

A Comparison of Physiochemical Property Profiles of Development and Marketed Oral Drugs

J. Med. Chem. 2003, 46, 7, 1250–1256

Relating Molecular Properties and in Vitro Assay Results to in Vivo Drug Disposition and Toxicity Outcomes

J.Med. Chem. 2012, 55, 14, 6455–6466.