  Despite improved rational drug design and a remarkable progress in genomic,
proteomic and high-throughput screening methods, the number of novel,
single-target drugs fell much behind expectations during the past decade.
Multi-target drugs multiply the number of pharmacologically relevant target
molecules by introducing a set of indirect, network-dependent effects. Parallel
with this the low-affinity binding of multi-target drugs eases the constraints
of druggability, and significantly increases the size of the druggable
proteome. These effects tremendously expand the number of potential drug
targets, and will introduce novel classes of multi-target drugs with smaller
side effects and toxicity. Here we review the recent progress in this field,
compare possible network attack strategies, and propose several methods to find
target-sets for multi-target drugs.
