Thursday, April 4, 2013
Automated SAR studies.
Desai et al. at Cyclofluidic Ltd. have
demonstrated the automated optimization of kinase inhibitors in an integrated
synthetic and analytic chemistry platform.
In this scheme,
derivatives of a parent compound are synthesized en masse on a microfluidic
matrix [a], purified by liquid chromatography and mass spectrometry [b]
and then assayed in vitro for inhibitory activity against the desired
target [c]. A computer program [d] interprets the assay results
and suggests further derivatives expected to improve the activity of the best
hits, which serve as starting points for the next round of synthesis and screening.
The cycle repeats until the operator has obtained SAR-optimized lead compounds
with in vitro pharmacokinetics superior to those of the parent compound.