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Project

ADME study of lead ferroptosis inhibitor which blocks organ injury and neurodegeneration in mice.

Ferroptosis is an iron-catalyzed form of regulated necrosis, which is shown to be detrimentally involved in several experimental disease models, such as acute kidney/liver injury and neurodegeneration. Glutathione peroxidase 4 (GPX4) is the central enzyme protecting the cell from excessive lipid peroxidation, which is the key execution process in ferroptosis. A high-throughput screening performed by the Stockwell Lab (Columbia University, US) led to the discovery of ferrostatin-1 (Fer1) as a potent in vitro inhibitor of ferroptosis. In vivo however, the molecule suffers from instability. Therefore, we developed ferrostatin-analogues with improved efficacy, solubility and stability. Ongoing research, in the framework of an FWO research project and an FWO-EOS project, illustrates that our patented lead Fer1--analogue UAMC-3203 is superior as compared to the benchmarks in several ferroptosis-driven experimental disease mouse models. The aim of this project is to study aspects of absorption, distribution, metabolism and excretion of the potential lead ferroptosis inhibitor UAMC-3203 in mice and rats. The results of this POC project should deliver an extended ADME-profile, verify its ability to cross the blood-brain-barrier and validate the possibility to administer UAMC-3203 orally. This will increase the valorisation potential of this compound. As the number of potential applications is relatively big, building a spin-off case for evaluation by seasoned investors and business professionals is likely the most suitable valorisation strategy.
Date:3 Feb 2020 →  30 Jun 2021
Keywords:FERROPTOSIS, PHARMACOKINETICS, BIOANALYSIS
Disciplines:Drug discovery and development not elsewhere classified, Pharmacokinetics