26th October 2019

The Beatson Drug Discovery Unit (DDU) has recently entered into a collaboration with Novartis to progress its ground-breaking work on the development of KRAS inhibitors.

KRAS belongs to a family of proteins commonly mutated in cancer. The genetic instructions for RAS proteins are altered in 30% of all cancers, and mutations are even more frequent in lung, colorectal and pancreatic cancer. These changes drive KRAS to be constantly active – similar to a stuck key on a keyboard - instructing cells to divide uncontrollably and produce more and more cells. In some cancer types, KRAS mutations are particularly aggressive and are linked to a higher number of cancer deaths.

For many decades, it has been difficult to find a direct pharmacological approach to target RAS proteins and they have been labelled 'undruggable'. While targeting direct binding with KRAS, the Beatson DDU has managed a significant breakthrough building on their leading expertise in fragment and structure based drug design. This drug development strategy screens a library of very small molecules called fragments and aims to identify binding pockets to target on the protein that will enable us to stop KRAS functioning in cancer patients. Using X-ray crystallography and computational chemistry, our chemists aim to grow these fragments into powerful and potentially effective drugs that can be used safely in clinical trials.

Through a negotiation with Sixth Element Capital, the fund manager for the Cancer Research Technology Pioneer Fund (CPF), Novartis will work together with the Beatson DDU to develop KRAS inhibitors further and has the option to exclusively licence certain drugs arising from this partnership. Novartis is making an upfront payment to CPF but will also contribute to funding ongoing research in the DDU for the duration of the collaboration, alongside continued support from CPF and CRUK. This will bring additional technical expertise and resources to the project, accelerating the delivery of potential drugs to benefit cancer patients.

Click here to read more from Cancer Research UK.