Ferroptosis-modulating natural products and their mode of action:
Targeting Redox Signaling
Ferroptosis is a form of regulated cell death discovered in 2012 that has great potential for novel approaches in the therapy of degenerative diseases and (drug-resistant) cancer. The number of proteins involved in ferroptosis is continuously growing, as is the number of small molecules that interfere with ferroptotic pathways. Challenges in targeting ferroptosis arise from interference with redox-dependent signaling cascades whose regulatory mechanisms - unlike kinase signaling cascades - are less studied and not fully understood. The development of drug candidates targeting ferroptosis is still in its infancy and many questions remain unanswered:
- How to design target-selective ferroptosis inducers? Are multi-target compounds of advantage?
- Which ferroptotic pathways are predestined targets against therapy-resistant cancer?
- How does ferroptosis achieve selective cancer cell lethality?
- What is the basis for the synergism between ferroptosis inducers and conventional chemotherapeutics?
Harnessing the enormous structural diversity of natural products could help to answer these questions, identify novel targets, and unravel molecular mechanisms.
Subprojects:
- Bioactivity-guided isolation of ferroptosis-modulating biogenic small molecules
- Ferroptosis-inducing compounds for anti-cancer therapy
- Ferroptosis-inhibiting compounds for the treatment of degenerative diseases and organ injury
- Identification of molecular targets and definition of (redox-dependent) signaling pathways
- Dissection of structural requirements