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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 as well as (drug-resistant) cancer. The number of proteins involved in ferroptosis is continuously growing as are 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 investigated and not completely understood. 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 lethality of cancer cells?
  •  What underlies the synergism between ferroptosis inducers and conventional chemotherapeutics?

Exploiting the enormous structural diversity of natural products might help to answer these questions, identify novel targets and unravel molecular mechanisms.

 Projects_7-ferroptosis

 Team: Solveigh Koeberle, Minh Bui Hoang


Subprojects:

  • Bioactivity-guided isolation of ferroptosis-modulating natural compounds.
    • Ferroptosis-inducing compounds as anti-cancer therapy.
    • Ferroptosis-inhibiting compounds for the treatment of degenerative diseases and organ injuries.
  • Identification of molecular targets and define (redox-dependent) signaling pathways.
  • Dissect structural requirements.


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