ACS was very intensive as always, me and Ferenc had 4 oral and 5 poster presentations, which you can check here. The most interesting topics for me were the ones trying to offer new strategies to improve the productivity of the drug discovery pipelines:
Physicochemical property profiles
One significant direction is to improve the physicochemical properties (or at least not significantly worsen them) during optimization. The presentations of Ernesto Freire and George Keseru emphasized that hits and leads should be optimized enthalpically rather than entropically (i.e. more H-bonds, less hydrophobicity) to get more favourable ADMET profiles (less toxicity, more selectivity, etc.). It is argued that clinical failures are primarily due to the unsuitable pharmacokinetic profile of the drug candidates (too hydrophobic, not soluble, etc.). The reason of the failures is either toxicity (because of the lack of selectivity), or the lack of effect (again caused by the small therapeutic window).
The other interesting direction sounds somewhat contradictory to the previous wave. Phenotypic screening is about finding molecules that showing the exact therapeutic effect we need. It is somewhat against the target-based approach, as it is not looking for compounds acting on a single target. On the contrary, the more targets (involved in the systems biology of the disease) it hits, the better. This approach says just the opposite of the first direction. Non-selective ligands are welcome here and to have an effect on multiple targets one would probably go for something hydrophobic, which will lack specificity. Chris Lipinski argues that most successful drugs hit many targets (e.g. kinase inhibitors).
I'm very much looking forward to see which direction will deliver more new drugs to the market in future.
|Philly vs. Vienna|
Right after the ACS I attended the EuroQSAR conference in Vienna: nice meeting, great people, interesting talks. Interesting case studies and some new approaches have been presented there. Some of the major software companies were also exhibiting, and we discussed potential integration strategies with them. We are currently discussing the details with many of them, so the list of tools waiting for integration is getting longer and longer. Which is a good thing.
In the meantime, the mcule team has been working hard, and a major release is coming up! Short list of what you can expect to appear on the mcule drug discovery platform soon: first subscription packages, improved visualization (incl. binding site and docking poses), user molecule upload, bulk exact search, product filter, and more.