Assessment of the Integrity of Compounds Stored in Assay-ready Plates Using a Kinase Sentinel Assay.

Assessment of the Integrity of Compounds Stored in Assay-ready Plates Using a Kinase Sentinel Assay.
Comb Chem High Throughput Screen. 2013 May 6;
Authors: Chen A, Zhao X, Mercer L, Su C, Zalameda L, Liu Y, Lembke A, Eastwood H, Dang S, Oung T, Xia X, Young SW, Xiao S, McCarter JD
Abstract
Sentinel assays are a convenient adjunct to LC-MS purity assessment to monitor the integrity of compounds in pharmaceutical screening collections over time. To assess the stability of compounds stored both at room temperature and at -20oC in assay-ready plates that were either vacuum pack-sealed using a convenient industrial vacuum sealing method or individually sealed using conventional foil seals, a diverse collection of ~ 5,000 compounds was assayed using a robust biochemical kinase assay at intervals over a one year period. Assay results at each time point were compared to those of initial assay using a series of correlations of compound Percent of Control (POC) values as well as IC50 values of a subset of compounds in 200 nL or 500 nL plates. The fraction of hits in common between initial assays and assays at later time points ranged from 82% to 95% over one year and remained relatively constant over time with all storage temperatures or sealing methods tested. A majority of the hits that exhibited a consistent gradual trend to lower potency over one year storage were shifted to lower potency upon the rapid removal of DMSO solvent. Compound precipitatio...

Source: Combinatorial Chemistry and High Throughput Screening - May 6, 2013 Category: Chemistry Authors: Chen A, Zhao X, Mercer L, Su C, Zalameda L, Liu Y, Lembke A, Eastwood H, Dang S, Oung T, Xia X, Young SW, Xiao S, McCarter JD Tags: Comb Chem High Throughput Screen Source Type: research