Project title: Early Drug Discovery to identify novel inhibitors of Prenylcysteine oxidase 1 (PCYOX1), a novel target in cardiology and oncology
Start/end date: 30 august 2024 – september 2026
Funding Agency/Programme: Italian Ministry of Health – National Recovery and Resilience Plan (NRRP) – Mission 6 – Component 2 – Investment 2.1. Strengthening and enhancing biomedical research in the NHS_CALL 2023
Partnership: Istituto Europeo di Oncologia (Applicant – UO1); Centro Cardiologico Monzino (partner – UO2); Fondazione Ri.MED (partner – UO3); Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione – ISMETT (partner – UO4).
Abstract: Prenylcysteine oxidase 1 (PCYOX1) is a candidate target in cardiovascular and metabolic disorders. Previous evidence by the team shows that PCYOX1 can be found associated with plasma lipoproteins (mainly pro-atherogenic VLDL and LDL), and that its pro-oxidant activity is involved in the generation of reactive oxygen species (ROS) which play a role in the development of atherosclerotic plaques. Moreover, PCYOX1 has proven to be a key regulator of adipogenesis, and acts upstream of critical adipogenic factors. More preliminary results extend the interest of PCYOX1 beyond these disease areas, as the function of PCYOX1 seems to be critical for the ability of tumor cells to acquire a “pro-metastatic” phenotype both in vitro and in vivo. Taken together, these evidences make PCYOX1 a relevant target for most frequent diseases. The project aims to validate the druggability of PCYOX1 and identify potential hit compounds directed against it for the future development of cardiovascular and anticancer drugs.
Ri.MED UO: Medicinal Chemistry
Ri.MED Principal Investigator: Maria De Rosa
Other Ri.MED collaborators: Ugo Perricone, Simona Di Martino