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Professor Chas Bountra is interested in identifying and validating target proteins for drug discovery. Various technologies and strategies have allowed him to progress promising clinical candidates into Phase I, II, III studies, and to market. These new drugs offer novel treatments for neurodegenerative and gastrointestinal diseases, as well as pain disorders.

Jonathan Webb: You only have to step into your local chemist to see how far medicines come over the last 100 years. Life changing drugs that were once unthinkable like antibiotics or insulin, or the contraceptive pill are now commonplace. But there's still an awful lot we don't know about the medicines that we all take. Consider your average packet of paracetamol. Now we know that these work to cure headaches and pains and we know that they're relatively harmless in small doses. But scientists still don't really know exactly how they work. And if we don't know how existing drugs work, then how do we design better ones?

The truth is that despite all of this drug companies are struggling to keep up with the rising demand for new medicines. And that's because what we call the drug discovery pipeline is costly, competitive and slow.

Chas Bountra: Drug Discovery is incredibly difficult, it's incredibly expensive, and it's incredibly challenging. The fact that we have not discovered as many drugs as we would have liked is not for one to try.

Jonathan Webb: Drug development has always been a risky business. Nine out of 10 drug development programmes will fail at the first investigation in patients, and those that do succeed can end up costing billions of pounds. These risks are tempered by the potential for big rewards luring academics and industry to develop the best new drugs against the hottest new targets. But there's a problem because competition starts at a very early stage. Traditionally, once a potential target has been found, academics and industry will work in strict secrecy, in an often decades-long race to market, which in 90% of cases will ultimately fail.

In order to deliver new medicines to hospitals and high street shelves, researchers and drug companies need to work together to speed up the process of drug discovery. By opening up access to newly discovered protein structures and drug targets, Oxford researchers are doing just that.

Chas Bountra: We've decided only to work on completely novel proteins, because it's by working on novel proteins where we generate truly novel medicines, and that's what society needs. So what we do for those proteins is work out the 3d X ray structure of that protein. And then we use those structures to design small molecule modulators. So things that are going to modify that protein. But what makes us I think pretty unique is that all of those reagents, you know, which are going to essentially facilitate drug discovery, we make them freely available. We give them away to any academic any biotech any pharma because we believe that's the best thing we can do to facilitate science and therefore facilitate drug discovery.

Jonathan Webb: X-ray crystallography enables the shape of a protein to be revealed, and has transformed the way that scientists design drugs. Continuously new structures are solved, new drugs are designed and new medicines are created. An example of this impact is improved HIV therapy resistance, and side effects to early treatments have prompted the development of a new class of drugs called non-nucleoside reverse transcriptase inhibitors. Using X-ray crystallography David Stuart and colleagues produced structures of these drugs, interacting with their HIV target.

Today, these inhibitors are included in the recommended first combination treatment for HIV. Recent experiments have led researchers at the structural genomics consortium in Oxford, to identify a drug called Jq1 as a potential new treatment for patients with a type of carcinoma. This drug is currently undergoing clinical trials to test its effectiveness and safety in humans, which could ultimately result in better survival rates.

This culture of collaboration and openness will ultimately revolutionise the way that basic research feeds into drug discovery, and that will improve clinical outcomes for us and for future generations. The really exciting thing is that all of this and more is happening right here in Oxford.

 

 

Revolutionary Biology

NDM celebrates the International Year of Crystallography. Our documentary series Revolutionary Biology explains how the field of structural biology has developed over the past 100 years, Oxford's involvement in that development, and where we go from here!

Part 1: The building blocks of life

Part 2: The history of structural biology

Part 3: Advanced technology

Part 4: A new age of drug discovery

You just have to step into your local chemist to see how far medicine has come over the past 100 years. Life-changing drugs, which were once unthinkable – like antibiotics, insulin and the contraceptive pill - are now commonplace.

But there's still so much we don't know about the medicines we take.

Drug companies are struggling to keep up with the rising demand for new medicines because of the competitive, timely and costly nature of the drug discovery pipeline. In order to deliver new medicines to the people who need them the most, researchers and drug companies need to work together to speed up the process of drug discovery.

By opening up access to newly discovered protein structures and drug targets, Oxford researchers are doing just that.

Translational Medicine

From Bench to Bedside

Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.