Discovery and validation of novel protein lipidation drug targets in cancer

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Lipidation is a rich and widespread class of protein post-translational modification (PTM), with key roles in signalling, cell death, immunity, protein stability and trafficking. More than 150 oncoproteins and potential cancer drug targets are lipidated, including many not amenable to traditional drug discovery. Intervening in the extensive network of enzymes regulating protein lipidation presents a unique opportunity to target these 'undruggable' proteins, an approach recently validated with the first FDA approval of a lipid transferase inhibitor in 2020. We have developed chemical proteomic technologies to study all the major classes of protein lipidation and delivered target validation and novel lipidation inhibitors into preclinical development for oncology, founding Myricx Pharma in 2019 to translate our findings into first in class therapeutics to benefit cancer patients. In this project, in collaboration with scientists at the Francis Crick Institute, Institute of Cancer Research (ICR) and in industry working on development of lipidation inhibitors in cancer, we will apply chemical probe design, chemical genetics, proteomics, and mechanistic drug target validation using modern gene editing and screening approaches to identify and validate novel targets for cancer therapy.