17 research outputs found
Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.
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.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2
Compound heterozygous BRAT1 mutations cause familial Ohtahara syndrome with hypertonia and microcephaly
Crystal structure and mutation analysis revealed that DREP2 CIDE forms a filament-like structure with features differing from those of DREP4 CIDE
Hypoxia influences linearly patterned programmed cell necrosis and tumor blood supply patterns formation in melanoma
Identification of unique binding site and molecular docking studies for structurally diverse Bcl-xL inhibitors
Interaction mode of CIDE family proteins in fly: DREP1 and DREP3 acidic surfaces interact with DREP2 and DREP4 basic surfaces
Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A
Dynamics of Bcl-xL in Water and Membrane: Molecular Simulations
10.1371/journal.pone.0076837PLoS ONE810-POLN