Inhibiting protein-protein interactions 1

Published on April 2, 2014   41 min

A selection of talks on Biochemistry

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Hello, my name is Adrian Whitty. I'm an associate professor of chemistry in the Department of Chemistry at Boston University. But before I came to BU five years ago, I worked in industry in drug discovery for about 15 years. And so my research programs at Boston University are very much guided by what I learned about how to develop drugs in an industrial setting. What I want to talk about today is the problem of how to develop small molecule inhibitors against a very challenging class of drug targets, called protein-protein interactions.
So, I'm going to start by talking about why one would even want to inhibit protein-protein interactions, in the first place.
On this slide, we see an analysis that was published by Hopkins and Groom, about 10 years ago, in which they have analyzed all of the proteins that make up the human proteome, and attempted to determine what fraction of those fall into the classes of protein families that we know we are able to discover small molecule inhibitors for, using contemporary drug discovery technology. And, what this slide shows is that, it's estimated that about 10% of the gene products in the human genome are biologically compelling as drug targets. They're involved in diseases, and, therefore, potentially drugs targeting those proteins could be beneficial in disease states. What Hopkins and Groom determined is that, only a fraction of those biologically compelling drug targets fall into families that we know how to find inhibitors four. And the majority parts of other protein families, where there is no current precedent for identifying small molecule inhibitors that can act as drugs. And a large fraction of these disease modifying genes, that are not part of conventionally druggable gene families, are protein-protein interactions.