Literature Update: Modeling potential toxicity for kinase inhibitors
Here is a 2010 paper that somebody shared with me recently - a really nice example of the application of computer modeling to real world problems in drug disocvery and development. A research group at the University of Chicago have developed a computer model of the realtionship between adverse events that occur during kinase inhibition therapy, and the actual kinase targets. In addition to predicting sets of clinically established adverse events (such as diarrhea and rash in patients treated with ERGFR inhibitors), the model was also able to predict sets of adverse events that had been documented, but that had not been so widely reported in publicly available clinical data. Here is the abstract for the paper:
"Kinase inhibition is an increasingly popular strategy for pharmacotherapy of human diseases. Although many of these agents have been described as “targeted therapy”, they will typically inhibit multiple kinases with varying potency. Pre-clinical model testing has not predicted the numerous significant toxicities identified during clinical development. The purpose of this study was to develop a bioinformatics-based method to predict specific adverse events (AEs) in humans associated with the inhibition of particular kinase targets (KTs)."
The full text of the paper is also available online at the NIH.
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