Mount Sinai School of Medicine
April 24, 2012
Do we know how drugs work? A systems biology perspective.
The high-value molecular target model for the therapeutic and toxic effects of drugs derives from classical pharmacology and biochemistry. The decreasing success rate of this academic-industrial enterprise may in part be the result of limitations of this model. An alternative view is that the effects of drugs result from their modulation of the activity of molecular networks within cells. We have shown, for example, that the effects of hallucinogens such as LSD and of antipsychotic drugs can be predicted not from their targets, but instead from their subtle alterations of the relative balance of molecular network activity in target cells in the brain (Neuron 2007 PMID:17270739, Nature 2008 PMID:18207054, Cell 2011:22118459). Another potentially important but relatively unrecognized basic mechanism of information encoding of data transmitted through molecular networks of cells is the pattern of activation of molecular components. Recent work on understanding the encoding of interleukin signaling information by duration of transcription factor activation in immune cells and the mechanisms underlying decoding of gonadotropin-releasing hormone pulse frequency-encoded information in the pituitary gonadotrope cell will be discussed.