One of the things I did at FBLD2012 was count how many fragments were in the libraries people were reporting on. Now, we all know that libraries are dynamic and not static, but I thought the numbers would give an idea of how big libraries are across the industry (and academia). I may have missed some, but these are the ones I caught:
Pfizer: 3000-5000 cpds @30mM in DMSO with 50-100 mg of powder in supply
GSK: 2400 cpds @100mM in DMSO. ~14 HA average for their "regular" library
~1000 cpds for NMR purposes
~1500 19F cpds
Selcia (Not sure if this is their library or the one they ran for a client, somebody with better notes?)
1500 cpds @30mM DMSO, purity >95%
Roche: 6900 cpds
Elan: 5260 cpds
Heptares: 4500 cpds, average HAC 16
Amgen: 1200 19F cpds
ZoBio: 1500 cpds
CSIRO: 480 cpds
Emerald ~2000 cpds
U Cambridge: 1300 cpds
Genentech: 2500 cpds
Ariad 735 Ro3 compliant cpds
Vanderbilt: 11000 cpds
Abbott: ~10000 cpds
Merck: ~10000 cpds
Plexxikon: 20000 scaffolds (explicitly differentiated from fragments in the talk)
Does anyone sell 19F libraries for academic purposes? Or are there any libraries that are more 19F rich that are commercially available?
ReplyDeleteI believe there are some commercial 19F libraries, or ones that can be easily created. Email me.
ReplyDeleteWhat do we learn when we look at these numbers? Are some companies more keen because of their bigger libraries or just lazy and adding more and more compounds without looking at diversity? What is the best method to screen so many compounds within a short period of time? What fragment criteria are really useful to look at?
ReplyDeleteThe Selcia fragment library is approximately 1500 compounds @ 30mM in DMSO, >95% purity but more importantly we have measured solubility >1mM in aqueous buffer. We noticed that predicted solubility had very little correlation with the measured solubility results! How many people measure solubility?
ReplyDeleteGood point Carol. I have also learned from the FBLD conference that Maybridge has an Ro3 library of 2500 compounds. These have also been validated for solubility at 1 mM in aqueous buffer (containing 0.5% DMSO).
ReplyDeleteThe Vernalis library is ~1400 compounds, tested for solubility in aqueous buffer (0.5-2mM) and stored at 200mM in d6-DMSO. The DMSO stocks are QC'd annually, and any compounds which have degraded are either removed or repurchased.
ReplyDeleteThe other thing that we do, which I regard as incredibly important, is to check the stability and solubility after 24 hours in aqueous solution. You'd be suprised how many compounds that you might consider for inclusion in a fragment library aren't stable in water.
I was involved in putting together the AZ 20k library a few years ago and I'll discuss some of that in a blog post (in the next week or two) rather than doing a long comment here.
ReplyDeleteAlthough aqueous solubility can be difficult to predict accurately for an arbitrary compound, the risks associated with of assuming adequate aqueous solubility are relatively low for ionised and polar compounds. We did measure aqueous solubility for a proportion of the library (I can't remember what this was) and used the data to assess risk or poor solubility as a function of ClogP.
Predicted solubility depends on the method used to make the prediction and a poor correlation with experiment using one method does not mean that the prediction using another method is necessarily inaccurate. This said, solubility is definitely an issue and you need to be thinking about solubility in DMSO as well.
Chem-X-Infinity offers fragment compounds and small organic compounds with a large diversity.
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