The Cancer Research UK Newcastle Drug Discovery Unit (2021-2025)

Background: The CRUK Newcastle Drug Discovery Unit (DDU) is an integrated, interdisciplinary team of cancer biologists, pharmacologists, structural biologists and medicinal chemists developing novel cancer treatments.

Anticancer drug design is well established in Newcastle, the DDU has played a pivotal role in the discovery and development of two medicines licensed in the previous quinquennium.

The same period has seen two further compounds originating from Newcastle programmes entering clinical trials, including the first compound to emerge from the Unit’s productive portfolio alliance with Astex Pharmaceuticals.

The current leadership and research team assembles experience from industry and academia to conduct internationally competitive drug discovery.

Aims: We aim to identify novel, differentiated small molecule drugs that address unmet clinical needs, using cutting edge technological approaches.

Our ambition for this quinquennium is to deliver at least one additional candidate medicine and experimentally evaluate 10 new target hypotheses. Methods: We develop and apply technologies to address challenging cancer targets.

We work with clinical colleagues and fundamental bioscientists from Newcastle and the wider cancer community to identify targets and apply comprehensive bioinformatic tools to assess their relevance to a significant patient population.

We repeat and extend published target validation results using diverse genetic manipulations and pharmacological tools, exploiting access to clinical samples where this helps to model disease and healthy tissue behaviour.

We conduct hit-finding screens either in house or collaboratively with partners, with a focus on structural and biophysical fragment-based approaches that use our strengths in synthetic chemistry and structural biology to develop and apply novel methodologies.

Structure-based screening and molecular design are at the heart of our approach to iterative medicinal chemistry to develop hits into drugs.

As hits are elaborated, they are assessed in biochemical and biophysical assays, and progressed to sophisticated disease models to verify their mechanism of action and demonstrate the anticipated anti-cancer activity.

How the results of this research will be used: The key outputs of this research will be candidate drugs for the treatment of patients with advanced cancers.

We will continue to develop technology to enhance the productivity of drug design: the protocols and reagents we develop constitute further results that will be used by the wider drug discovery community.

Our programs will also result in probe molecules that will be used to dissect the roles of specific targets in normal and diseased tissue.