Integrated analysis of drug-induced gene expression profiles predicts novel hERG inhibitors.

ABSTRACT: Growing evidence suggests that drugs interact with diverse molecular targets mediating both therapeutic and toxic effects. Prediction of these complex interactions from chemical structures alone remains challenging, as compounds with different structures may possess similar toxicity profiles. In contrast, predictions based on systems-level measurements of drug effect may reveal pharmacologic similarities not evident from structure or known therapeutic indications. Here we utilized drug-induced transcriptional responses in the Connectivity Map (CMap) to discover such similarities among diverse antagonists of the human ether-à-go-go related (hERG) potassium channel, a common target of promiscuous inhibition by small molecules. Analysis of transcriptional profiles generated in three independe

SUBMITTER: Babcock JJ 

PROVIDER: S-EPMC3720659 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature