Welcome to the latest issue of Drug Discovery Today, Editors Choice. I hope you have enjoyed the previous issues in this new format. I’d be grateful for any suggestions or feedback on this new style emailing. Feel free to contact me on s.carney@elsevier.com
In this issue we feature 3 interesting articles, the first by György G. Ferenczy and György M. Keseru who discuss Thermodynamics guided lead discovery and optimization. This article outlines how normal lead optimization processes can often involve detrimental changes in physical properties. They propose that by using thermodynamics it seems that enthalpy-driven optimization produces higher quality leads.
The second article by Masaya Orita, Kazuki Ohno and Tatsuya Niimi examines another approach in their paper: Two ‘Golden Ratio’ indices in fragment-based drug discovery’. They examine the ratios of size of the fragment:final lead compound, which has been proposed to be useful in library design, and a second index related to maximum ligand efficiency. Both of these indices are based upon the ‘golden ratio’ and may be of use in library design and streamlining the hit-to-lead process.
Finally, the article by Scott D. Bembenek, Brett A. Toungeand Charles H. Reynolds follows on from the Orita paper in that it is concerned with the use of Ligand Efficiency in fragment-based approaches to lead generation. They evaluating FBDD examples from the literature using LE and fit quality, and found that, in general, the LEs of starting fragments are greater than those of larger, more elaborated, structures. Fit quality scores, however, tend to improve upon optimization of the fragments.