Anticipating drug side effects by comparative pharmacology.
BACKGROUND
Anticipating the likely side effect profile of drugs is an aspect of key importance in current drug discovery, development and marketing. It was recently shown that drug pairs having similar side effect profiles had also affinity for a common target. Acknowledging that most drugs have a rich polypharmacology, we provide proof that drugs related by side effect similarity have in fact affinities for multiple common targets beyond their primary targets and set the basis for the use of comparative pharmacology to anticipate drug side effects.


METHODS
Nomenclature issues to be able to identify and properly store drugs, targets and side effects from multiple public sources; the construction of drug networks from side effect similarity and the inference of common targets among them; polypharmacology and data completeness; methods for in silico target profiling; and comparative pharmacology and inference of common side effects.


RESULTS
The reader is provided with a detailed step-by-step analysis of the entire process from predicting the target profile of a compound to anticipating its side effect profile, and a discussion on the particular needs and limitations found at each stage of the process through illustrative examples.


CONCLUSIONS
Comparing preclinical pharmacology data obtained in vitro but also predicted in silico using modern virtual screening methods represents an attractive strategy to anticipate clinical drug side effects.
Garcia-Serna
Ricard
R
Chemotargets SL, Passeig de Circumval.lació 8, 08003 Barcelona, Catalonia, Spain.
Mestres
Jordi
J
D017076:Computer-Aided Design; D016503:Drug Delivery Systems; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010600:Pharmacology / Q000379:methods*