GSK
University of Strathclyde

The development of molecular glues to target previously untreatable cancer proteins

Targeted protein degradation (TPD) is an emerging approach to treating disease, which works by selectively targeting and removing disease-causing proteins previously considered ‘undruggable’. Many of these hard-to-target proteins play key roles in cancer and inflammatory diseases, areas where current treatments are often lacking. These proteins are called “undruggable” because they lack specific binding pockets, that common drugs need to latch onto. TPD overcomes this challenge in two common ways, one of which is the focus of Alex’s work, which uses unique small molecules called molecular glue degraders.

Alex’s research focuses on a cancer-related protein which is frequently over-produced and considered a key target for cancer therapy. His project aims to optimise the use of molecular glue degraders to selectively and effectively target his protein of interest for breakdown. An approach that could lead to the development of low-dose, chemotherapy free, oral cancer treatments.

However, while the protein of interest is a valuable therapeutic target, its unintended degradation can also occur as a by-product when designing drugs to degrade other disease-causing proteins. This off-target effect poses a significant challenge across the TPD field. To address this, Alex’s work also aims to uncover how unintended degradation of the protein of interest can be avoided.

By tackling both the optimisation of degraders and the broader selectivity challenges in TPD, Alex’s project seeks to deliver critical insights that will benefit drug discovery efforts across the pharmaceutical industry. Furthermore, his research will also investigate other ‘undruggable’ cancer targets and take advantage of high-throughput chemistry direct-to-biology techniques to rapidly discover novel degraders.

Biography:

Prior to his PhD, Alex received a First-class master’s in chemistry from the University of York, with a year abroad. Alex developed an interest in medicinal chemistry and drug discovery during his undergraduate degree and whilst working at the Centre for Targeted Protein Degradation (CeTPD) for two years following his master’s. From this experience, Alex decided to continue his studies in the GSK and University of Strathclyde PhD programme. During the first year and a half of his PhD, Alex has been awarded a joint first-place prize in the 2024 SCI Scotland Postgraduate Research Competition, in addition to being a finalist at STEM for Britain 2025, where he presented his research in the Houses of Parliament. Alex also won the first-place poster prize at the 2024 GSK / University of Strathclyde Postgraduate Symposium.