1 research outputs found
Investigating the Behavior of Published PAINS Alerts Using a Pharmaceutical Company Data Set
Biochemical
assay interference is becoming increasingly recognized
as a significant waste of resource in drug discovery, both in industry
and academia. A seminal publication from Baell and Holloway raised
the awareness of this issue, and they published a set of alerts to
identify what they described as PAINS (pan-assay interference compounds).
These alerts have been taken up by drug discovery groups, even though
the original paper had a somewhat limited data set. Here, we have
taken Lilly’s far larger internal data set to assess the PAINS
alerts on four criteria: promiscuity (over six assay formats including
AlphaScreen), compound stability, cytotoxicity, and presence of a
high Hill slope as a surrogate for non-1:1 protein–ligand binding.
It was found that only three of the alerts show pan-assay promiscuity,
and the alerts appear to encode primarily AlphaScreen promiscuous
molecules. Although not enriching for pan-assay promiscuity, many
of the alerts do encode molecules that are unstable, show cytotoxicity,
and increase the prevalence of high Hill slopes