Safran Zunft Challenge

Dan has already hit the highlights of FBLD 2014.  I won't do the lowlights.  They were few and far between.  I will try to give some flavor of the conference.  If you missed it, they t-shirts given out had this as a design

 

This was designed by Lukasz Skora of Novartis.  It is keywords used here at the blog, sized by frequency.  That is pretty cool.  It also gives us an idea of what we are really talking about here.  I have some other "flavor of Basel pictures" posted here.  

The conference was excellent, just the right size to allow people to interact at a high level.  The dinner was especially good for this (and the unending wine/beer didn't hurt!).   I have been lucky this year to be at many conferences with many different people.  Damian Young at the Baylor College of Medicine Center for Drug Discovery (and recently of the Broad) has been speaking at all of them about his Diversity Oriented Synthesis (DOS) approach to generating fragments.  Well, this has bothered me, DOS is not Fragments.  Am I some sort of Luddite?  Am I being too purist?  Could be.  

Well, an eminent group of FBLD-ers was gathered around a table during the conference dinner, including Justin Bower and Martin Drysdale of the Beatson, Chris Smith of Takeda, the aforementioned Dr. Young, myself, Terry Crawford of Genentech, and Beth Thomas of the CCDC.  So, out of this discussion, comes the Safran Zunft Challenge, administered by Dr. Bower.  I bet Damian that his molecules are too complex to be "fragments".  What will this mean?  I am betting that a "bad" interaction is worse than a good one, that is going all the way back to the Hann Model.  

So, this one molecule from Damian's presentation.  I have nothing against it per se, but for illustrative purposes.  I bet that his molecules will not have a LEAN (pIC50/HAC) >0.3.  [This is the metric I like, Pete.  I understand the limitations.]  By FBLD2016, Damian expects to have data on his molecules (and he is looking for partners).  If I lose, I owe the undersigned a beer.  Below we have preserved for posterity the discussion and those who were there (no hopping on the beer bandwagon late people!).  

I also think this is a good way for us to discuss the ontology of a "fragment"?  To me, its not just size, it is more of its "nature".  Fragments rely on simple molecules, adding complexity even with small molecules, strips away the "fragment-ness", IMNSHO.