Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Nat Rev Drug Discov 2016 08 11;15(8):533-50. Epub 2016 Apr 11.

Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0AH, UK.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.

Download full-text PDF

Source
http://dx.doi.org/10.1038/nrd.2016.29DOI Listing
August 2016
117 Reads

Publication Analysis

Top Keywords

inhibitors ppi
4
develop inhibitors
4
chemists develop
4
ppi inhibitors
4
inhibitors reached
4
development review
4
clinical development
4
reached clinical
4
medicinal chemists
4
efforts medicinal
4
work begun
4
states work
4
disease states
4
begun tools
4
tools classes
4
yield efforts
4
classes ppi
4
review describe
4
describe leading
4
examples successful
4

References

(Supplied by CrossRef)

AM Petros et al.
J. Med. Chem. 2006

DJ Huggins et al.
J. Chem. Theory Comput. 2011

T Clackson et al.
Science 1995

AA Bogan et al.
J. Mol. Biol. 1998

MC Smith et al.
Expert Rev. Mol. Med. 2012

P Chakrabarti et al.
Proteins 2002

O Keskin et al.
J. Mol. Biol. 2005

B Ma et al.
Proc. Natl Acad. Sci. USA 2003

FP Davis et al.
PLoS Comput. Biol. 2010

Z Hu et al.
Proteins 2000

FB Sheinerman et al.
Curr. Opin. Struct. Biol. 2000

Similar Publications