Fragment-Based Screening Reported Hits

Whilst there are a variety of techniques to measure the properties or diversity of fragment libraries it is interesting to look at the profiles of compounds that actually appear as hits in fragment-based screening campaigns. I’ve been compiling a database of compounds that have been reported as hits in the literature, this database now has >280 entries culled from 85 publications and might be expected to give some insight into the type of compounds that appear as hits. With the caveat that the dataset only includes information that has been published.

A profile of the physicochemical properties (HBD, HBA, PSA, HAC, LogP, LogD, MWt, RBC) was generated using an Applescript that uses evaluate to calculate the physicochemical properties and Aabel to construct the histograms. I also used it to determine pKa in order to identify acidic or basic groups and categorized the fragments accordingly, in addition I calculated the fraction of aromatic atoms (number of aromatic atoms/number of heavy atoms) since there has been concern about the number of aromatic compounds in fragment collections.

The results are shown in the collection of histograms below. One notable observation is that around 30% of the hits contain an ionisable group (pKa predicted using ChemAxon tools), the molecular weight is generally well below 250 with the heavy atom count (HAC) 15 or lower. The lack of rotatable bonds (RBC) and the relative high Fraction Aromatic scores are consistent with the observation that many of the hits are substituted aromatic or heteroaromatic rings.


This profile needs to be taken with a pinch of salt since you can only test what is available, it will be interesting to see if the efforts to design fragments with more 3D structure changes the profile of the observed hits.

Updated 18 November 2011
See also
Fragment Based Screening
See also
Fragment Collections
See Also
Fragment Collection Profiles
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