Challenge
Most protein:protein interactions occur within the cell and thus can only be targeted
by small molecules. Furthermore, PPI differ structurally from more classic drug
targets such as enzymes and receptors, and consequently existing compounds have
generally delivered disappointing results.
Therefore, new approaches are needed to develop novel small molecules which inhibit
PPI in cancer.
Aim
The objective of this project is to develop a series of innovative small-ligand
tools and libraries that allow new approaches to the inhibition of protein:protein
interactions in cancer.
A key theme is the utilization of structural motifs found in natural PPI inhibitor
compounds. This is coupled with high content testing of the resultant structures
on 3 distinct PPI targets relevant to different types of cancer, to allow compound
rule-sets to be developed and improved.
We want to develop small-ligand libraries focused on PPI inhibitors of relevance
to cancer. Furthermore, we will develop innovative tools that allow improved library
design in this area by integrating in-silico approaches, bio-informatics, new approaches
to compound synthesis and pharmacology.
The project will also cover the scientific areas such as in-silico prediction of
drug-like properties, prediction of ADME parameters, predictive toxicology and creation
of virtual libraries.