Subscribe in a reader

Cambridge MedChem Consulting

Trust but verify

There is an article in Nature describing a collection of problems that have arisen from incorrect chemical structures in biological screens DOI. I'm slightly surprised that this is regarded as newsworthy, but I guess it serves as a timely reminder.

The data from screening campaigns invariably contains errors

  • It is often a single point assay
  • Quality and diversity of Sample Collection is variable
  • Compounds may interfere with the detection system
  • False positives due to aggregation
  • High density plates can result in cross contamination, edge effects

There is a very simple mantra you should adopt when analysing screening data "Trust but verify".

  • Check compounds that were found active against the selected target are re-tested using the same assay conditions used during the HTS.
  • Does a resynthesised (not repurchased) show the same activity
  • Dose response curve generation: an IC50 or EC50 value is then generated, does it have a reasonable slope? Uneffected by incubation time.
  • Are related analogues available, check for genuine Structure-Activity Relationships


There is a strategy for the analysis of HTS data in the Drug Discovery Resources.