Rapid Identification of a Putative Interaction between β₂‐Adrenoreceptor Agonists and ATF4 using a Chemical Genomics Approach

A chemical genomics approach to drug reprofiling in oncology: Antipsychotic drug risperidone as a potential adenocarcinoma treatment

“…Elimination of 11 clones that also occurred in the negative control wells (no drug added) left 35 clones of interest. These were submitted to a selective elution experiment, as we have described previously [6,7] with a solution of free chlorpromazine. Significant elution in this experiment should indicate that a clone binds to unmodified drug as well as to a surface-modified analogue.…”

“…The Magic Tag® screen and enzyme kinetics studies used published methods [7,13,14]. For other experiments chemicals, drugs and cell line media were acquired from Sigma Aldrich, Cell lines were acquired from ECACC or ATCC.…”

“…Our Magic Tag® chemical genomics tool was designed to link the known biological activity of an organic chemical with the genome as expressed through a phage displayed library of polypeptides [6,7]. Herein we demonstrate that Magic Tag® has the potential to be a new and complementary method for systematically screening known drugs to identify reprofiling opportunities.…”

“…Known to have multiple protein targets, such drugs are interesting candidates for drug reprofiling. We decided to photoimmobilise one drug from this class, chlorpromazine 1, using Magic Tag® and screen it against a library of polypeptides displayed on T7 bacteriophage, as previously described [7].…”

“…Around 60% of D. melanogaster genes have human orthologs [12]. Significantly, around three quarters of genes related to human disease states have orthologs in D. melanogaster [7] and all major human signaling pathways are present in D. melanogaster [10].…”