Within the group, we typically work on up to three drug discovery projects with the ultimate aim of delivering preclinical candidates. These projects are at different stages and include early projects that are in the hit discovery phase, as well as a more mature project where we optimize advanced lead compounds to yield preclinical candidates.

In our current main drug discovery project, we are targeting a protein-protein interaction to deliver a new therapy for diffuse large B-cell lymphoma (DLBCL), a particular aggressive form of lymphoma. This project is in lead optimization and we work closely with the Target Evaluation and Molecular Therapeutics, the Cancer Pharmacology and Stress Response, the Hit Discovery and Structural Design and the Drug Metabolism and Pharmacokinetics groups at the ICR to achieve our aims.

We started this project by discovering weakly potent fragment-like hit matter. We optimized these starting points and discovered different chemical series including inhibitors that show IC50s in the low nanomolar range. We are currently optimizing these chemical series towards a preclinical candidate and at this stage put particular emphasis on optimizing the in vivo pharmacokinetic properties and pharmacodynamics effects. Throughout the project we have explored crystal structures and structure based design.

In addition to our drug discovery projects, different PhD projects are ongoing within the group. The key goal of Ellen’s project is to design and synthesise dual kinase bromodomain inhibitors targeting ALK and BRD4. This combination will target multiple pathways of cancer growth and survival in high-risk neuroblastoma patients. So far, Ellen has been successful in optimising a known dual inhibitor towards a dual ALK-BRD4 profile and is currently analysing the efficacy of the compounds in vitro.

Charlie Robertson and Will Darlow are also PhD students, working on bifunctional modulators to target cancer cells.