Protein-protein interaction inhibitors: case studies on Small Molecules and Natural Compounds.

The large size and variety of the human protein interactome and the obvious
relevance of the protein–protein interactions in every physiological function,
render protein–protein interactions at the same time an extremely challenging and
attractive target for developing of new therapeutic substances. A further interesting
aspect of targeting protein–protein interactions (PPI) for drug discovery is that, at
least in some cases, molecules directed against PPI may provide a way to overcome
the resistance mechanisms encountered for active site binding enzyme
inhibitors. The considerations above can be extended to bacterial and viral interactome,
further expanding the vastness and complexity of the subject of PPI
inhibition and modulation.
For these reasons, there is no surprise that targeting PPI has become a subject of
intense research activity in both industry and academia over the past decade.
Reviewing the literature and the available databases shows that over 150 small
molecule compounds have been found to inhibit about 20 PPI targets and that
some of these molecules have already reached, or are about to reach, the drug
market. As usual, these figures can have a double reading: the optimistic interpretation
is that these successes demonstrate the validity of the approach, while the
critics might say that the huge effort dedicated to find PPI inhibitors has resulted in
scarce results. The fact is that exploring PPI is a stimulating new subject of study
that is relevant for the basic knowledge on the chemistry of living organisms with
the important outcome to offer the possibility of opening a new era of drug
discovery.
This book is a collection of essays from Italian research groups from Industry
and University involved in drug discovery and, although the book presents different
subjects in each chapter, the unifying idea comes from our belief that only an
integrated approach of the different techniques nowadays available, may overcome
the challenges presented by this new frontier in drug discovery. For this reason, the book opens with reviews about the current status of the research on PPI in drug
discovery and goes on by presenting the state of the art in basic techniques like
computational tools, NMR, X-ray crystallography and FRET that, integrated, may
give the opportunity of success in this field.