Completed Genetics & Molecular Biology Cancer

The Cambridge Molecular Therapeutics Programme (MRC Programme 2)

In plain English

AI plain-English summary

Most new drugs fail because they target the wrong part of a protein. Enzymes—proteins that drive chemical reactions—have active sites that look nearly identical across many different enzymes, so drugs that block one active site often block others, causing side effects and poor results. This research team is developing a completely different approach: instead of blocking an enzyme’s active site, they aim to disrupt the physical interactions between proteins, which are far more specific and varied. They will build new methods to identify which protein-protein interactions to target, design drugs that break those interactions, and test those drugs on human cells to see if they work without harming healthy tissue. If successful, this work could transform how drugs are discovered, moving away from blunt tools that hit many targets toward precise molecules that only affect the disease-causing process. This is fundamental science—it does not promise a new drug tomorrow—but it rethinks the basic rules of drug design, with the potential to eventually produce treatments for cancer and other diseases that are more effective and far less toxic.

View original technical description
Most new drugs that affect DNA repair or mitosis target an important group of proteins called enzymes, by blocking a particular region (the ‘active site’) in them. However, human cells require multiple enzymes to function normally, and the ‘active sites’ of many of these are similar in structure. Therefore, drugs that block the active sites of enzymes are not sufficiently selective, leading to poor activity, and unwanted side effects in patients. We are developing new ways of making drugs, not by targeting the active sites of enzymes, but by disrupting interactions between proteins, which are necessary for cells to work correctly. We will not only devise methods to find the best targets to disrupt, but will also pioneer new methods to find drugs that disrupt these interactions, and find new ways to test the effect on human cells of the drugs we discover in this way, to evaluate their potential for further development. This work has the potential to transform the basic scientific research that helps us to understand human diseases, as well as the way new drugs are discovered and developed.

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Researchers

Ashok Venkitaraman (Principal Investigator)

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Original classification

Research Grant

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