To further explore the known relationship between a compound's gene expression signature and cell line genotype, we profiled the MDM2 inhibitor AMG-232 in a panel of ten MCF10A isogenic cell lines. We observed AMG-232 had a dramatic reduction in TAS only in the cell line in which TP53, which is negatively regulated by MDM2, was homozygously deleted compared to the other 9 cell lines which were all TP53 wild-type. This result may indicate the utility of a more general screening approach by which the potential target(s) of a compound could be identified by generating L1000 profiles across a diversity of genetic backgrounds.
