A5070345158- Cell death mechanisms and regulation
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- Drug Transport and Resistance Mechanisms
- Cancer-related Molecular Pathways
- interferon and immune responses
- NF-κB Signaling Pathways
- Trace Elements in Health
- Inflammasome and immune disorders
- Microtubule and mitosis dynamics
- Phagocytosis and Immune Regulation
- Cytokine Signaling Pathways and Interactions
- Amino Acid Enzymes and Metabolism
University of Antwerp
2015-2020
Ferroptosis is an iron-catalyzed, nonapoptotic form of regulated necrosis that results in oxidative lipid damage cell membranes can be inhibited by the radical-trapping antioxidant Ferrostatin-1 (Fer-1). Novel inhibitors derived from Fer-1 scaffold ferroptosis potently but suffered solubility issues. In this paper, we report synthesis a more stable and readily soluble series analogues inhibit ferroptosis. The most promising compounds (37, 38, 39) showed improved protection compared to...
Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated necrosis that critically dependent on glutathione peroxidase 4 (GPX4). It has been shown to contribute liver and kidney ischemia reperfusion injury in mice. A chemical inhibitor discovered by high-throughput screening displayed inhibition ferroptosis with nanomolar activity was dubbed ferrostatin-1 (fer-1). Ferrostatins inhibit oxidative lipid damage, but suffer from inherent stability problems due the presence an ester moiety....
Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation receptor-interacting protein kinases 1 3 (RIPK1/3) in a necrosome complex, eventually leading phosphorylation relocation mixed lineage kinase domain like (MLKL). Using high-content screening small compounds FDA-approved drug libraries, we identified anti-cancer Sorafenib tosylate as potent inhibitor TNF-dependent necroptosis....
Abstract The Aurora kinase family (Aurora A, B and C) are crucial regulators of several mitotic events, including cytokinesis. Increased expression these kinases is associated with tumorigenesis compounds targeting under evaluation in clinical trials (a.o. AT9283, AZD1152, Danusertib, MLN8054). Here, we demonstrate that the pan-Aurora inhibitor Tozasertib (VX-680 MK-0457) not only causes cytokinesis defects through inhibition, but also a potent necroptosis, cell death process regulated...
Receptor interacting protein kinase 1 (RIPK1) plays a crucial role in tumor necrosis factor (TNF)-induced necroptosis, suggesting that this pathway might be druggable. Most inhibitors of RIPK1 are classified as either type II or III inhibitors. This opened up some interesting perspectives for the discovery novel target active site RIPK1. Tozasertib, I pan-aurora (AurK) inhibitor, was found to show very high affinity Because tozasertib presents typical structural elements development...