Introduction

Many cancers are driven by proteins that scientists have historically been unable to target with medicines. These ‘undruggable’ proteins remain one of the biggest challenges in modern cancer research and limit the number of patients who can benefit from precision therapies.

Researchers at the University of Bath are developing new molecular technologies designed to overcome this challenge and expand the range of cancers that can be treated with targeted medicines.

Our approach

The project focuses on developing ‘covalent macrocycles’ – a new class of therapeutic molecules designed to bind tightly and selectively to difficult cancer targets.

Unlike conventional drugs, these molecules are engineered to recognise large protein surfaces involved in cancer signalling and form durable interactions with disease-driving proteins. This could enable researchers to target cancers that are currently resistant to existing therapies.

By combining synthetic chemistry, chemical biology, automation, and computational approaches, the research aims to open entirely new areas of therapeutic discovery

Aims and objectives

The project aims to:

Develop advanced technologies for rapidly generating large libraries of drug-like molecules
Discover new therapeutic molecules that target difficult cancer proteins
Expand the range of proteins that can be treated using precision medicines
Create screening platforms that accelerate early-stage cancer drug discovery
Develop more sustainable approaches to discovering future medicines

Initially, the research is focused on proteins involved in pancreatic cancer signalling, where treatment options remain limited.

Methods

The team is developing advanced screening technologies capable of generating and testing millions of molecules simultaneously. Using automated synthesis and high-throughput discovery platforms, researchers can rapidly identify promising therapeutic molecules that interact with difficult cancer targets.

The project combines expertise in synthetic chemistry, chemical biology, covalent drug discovery, structural biology, and computational molecular design to better understand how molecules interact with disease-driving proteins. By integrating these approaches, the researchers aim to accelerate the discovery of more selective and effective cancer therapies.

In the long term, the technologies being developed at Bath could provide a broadly applicable platform for discovering medicines against cancers and other diseases that currently lack effective treatment options.