Dual Inhibitors inspired from vitamin E (DIVE):
Towards vitamin E analogs that relieve inflammation by targeting mPGES-1 and 5-lipoxygenase without impeding resolution
Chronic inflammation is a hallmark of cancer, cardiovascular disease and neurodegeneration that is driven by pro-inflammatory lipid mediators, i.e. prostaglandin E2 and leukotrienes. Non-steroidal anti-inflammatory drugs (NSAIDs) suppress prostaglandin formation but are afflicted with severe side effects. Selective inhibition of microsomal prostaglandin E2 synthase (mPGES)-1, preferentially in combination with suppression of leukotriene formation, is considered as a safe alternative. We recently found that vitamin E metabolites along with various semisynthetic analogues accumulate in immune cells and relieve inflammation by targeting 5-lipoxygenase, seemingly without impeding resolution, and we revealed mPGES-1 as additional target. The aim of the DIVE project will be to design and characterize potent and balanced inhibitors of mPGES-1 and 5-lipoxygenase starting from endogenous vitamin E metabolites that retain the desired activity of NSAIDs while avoiding their drawbacks.
Collaboration Partners
- SONAS, University of Angers, France
- Department of Pharmaceutical/Medicinal Chemistry, University of Jena, Germany
- Department of Pharmacy/Pharmacognosy, University of Innsbruck, Austria
- Department of Pharmaceutical/Medicinal Chemistry, Paracelsus Medical University Salzburg, Austria
- Department of Pharmacy, University of Naples Federico II, Italy
- INSPIRE Group, University Hospital Jena, Germany
Project Funding
