This page contains information and questions from the Shaping a Screening File session and the responses provided.
Information on Shaping Screening Files
Plate-based diversity subset
- Ordering of a subset of compounds on a plate in order of physical properties
- Rule of 40
- All criteria are multiples of 40
- 200+ compounds on a plate
- Binned compounds on each plate
- Plate-based properties vs individual compound basis
- Aim for double coverage
- Computational problem for calculating this! Many permutations!
- Take top plates; best plates move to the top of the pile
- 17 iterations gave optimal order
Introduce molecular redundancy
- Relationship between molecular fingerprint to known active and chance of finding biological activity
- Belief Theory - work out molecules ended to find one active
- Defined ‘sure’ as 95% certainty of activity
- Probability of getting an active
Did you return to missed sample plates and find out why they were missed?
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No not done
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It was a very large screening file
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It is an interesting question, but not a question needed to be solved at the time
How many compounds do you need to screen?
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Validated structure and knowing it is important
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Knowing how much compound in a well is essential to calculate IC50 values
Have you done the PBDS in practice?
- Yes, became a major part of Pfizer’s work and economic considerations