Primary Screening Activity
With the assistance of Michael Jobling, head of compound management at Elan Pharmaceuticals, we conducted experiments to analyze how secondary recovery could positively impact drug screening results. We re-solubilized precipitated fragment samples back into solution in DMSO, and then sent 24 samples to primary screening.
The percent inhibition results were compared to the control group, which had visible precipitates at the bottom of the tubes and did not go through the ultrasonic secondary recovery process.
In the control experiment, 29% of the screened fragments showed less than 20% inhibition, 17% of the group showed 20–40% inhibition, 21% of the group showed 40–60% inhibition, 4% showed 60-80% inhibition, and 29% showed high activity with greater than 80% inhibition.
In the secondary recovery experiment, with precipitated samples recovered back into solution, the primary screening accuracy increased: 38% of the screened fragments showed high activity with greater than 80% inhibition, 12% showed 60–80% inhibition, and 17% showed 40–60% inhibition. The differences between the control and the secondary recovery experiments are summarized in Figure 3.
Fragments put through the Hendrix SM100 for secondary recovery increased activity by an average of 68% with a maximum increase in inhibition of 384%.