I wanted to give you guys a little something to think about, especially in light of the book coming out that I am involved with. Most of you have by now, or should have by now, read Alex Alex's paper in Current Topics in Med Chem from last year. It overall is a great issue (with a super duper paper on NMR in drug discovery by yours truly wink wink nudge nudge).
Alex's paper looks back at all of the fragment papers and looks at what was the starting point, where it went, etc. I took his data and applied my own filter to it (what one former colleague termed the ZOF, the Zartler Optical Filter).
The following two tables are from Chapter 2 of the upcoming book, on designing a fragment process.
This data is looking at the origin of the type of fragment strategy employed and the main method used to support it moving forward. Linking/assembly is exactly what it sounds like, attaching different fragments (zinc binding group and biphenyl a la Abbott). Anabolic is the logical growth of a fragment to a lead-like/drug-like molecule. Other could not be classified from Alex's paper.
There were roughly the same number of projects that used either anabolic or linking. However, the anabolic method would appear to be better at maintaining or increasing ligand efficiency.
I also looked at NMR vs. X-ray vs. Other methods in terms of projects that maintain or increase LE. NMR and X-ray have the same number of projects (whose sum is equal to the total of Other). It does appear that NMR is better than X-ray in maintaining LE.
Here is the firebomb: With the well documented history of success, sufficient data to say that the anabolic approach is superior, and the NMR approach superior to X-ray, why is it that large pharma seems to be so slow in adopting what is an obviously successful method?