Thesis Defence of Albert Antolin "The impact of polypharmacology on chemical biology"

On October, 9th at Marull Room (Dr. Aiguader 80, floor -1) at 12:00, Albert Antolin, member of the Systems Pharmacology group of GRIB will defend his thesis " The impact of polypharmacology on chemical biology". You are all invited to this event.


There is now ample evidence that drugs have biologically relevant interactions with more than one protein, a behavior that is commonly referred to as polypharmacology. This finding is starting to have a true impact on the drug discovery process, transforming it into a more holistic endeavor. In contrast, chemical biology continues to be a reductionist discipline, still regarding chemical probes as highly selective small molecules that enable the modulation and study of one specific target. In an effort to bring a more comprehensive perspective to the practice of chemical biology, this Thesis aims at demonstrating that chemical probes, like drugs, tent to bind to more than one protein, a behavior that may have confounded many of the biological insights gathered using these tool compounds. Accordingly, in this Thesis we use the Poly(ADP-ribose) polymerase (PARP) enzyme superfamily to illustrate the consequences that chemical probe polypharmacology have for the practice of chemical biology and follow-on drug discovery. Next, we extend this analysis to a collection of chemical probes to demonstrate the ubiquity of polypharmacology and we provide guidelines to derisk the practice of chemical biology using potentially promiscuous tool compounds. Chemical biology cannot continue to overlook the existence of polypharmacology and the results presented in this Thesis urge it to become a more holistic discipline that looks at the use of tool compounds from a systems perspective.

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