NecroFerrins as dual therapeutic inhibitors targeting necroptosis and ferroptosis
Abstract
Over the past two decades, increasing attention has been devoted to regulated forms of cell death that occur independently of apoptosis. Among these, necroptosis and ferroptosis exhibit a necrotic-like morphology, yet are defined by distinct molecular and biochemical signatures. Both pathways have attracted considerable interest due to growing evidence implicating them in the pathogenesis of a wide range of acute and chronic disorders. Notably, the simultaneous engagement of multiple regulated necrosis pathways has been reported in many disease contexts, highlighting the limitations of single-target therapeutic approaches. In this light, the design of multi-target-directed ligands, that is, embracing a polypharmacological strategy, has emerged as a promising direction for the development of future therapies. In this review, we propose the concept of NecroFerrins, a class of small molecules that simultaneously inhibit necroptosis and ferroptosis. Within this class, we identify RIPROStatins as a distinct subclass of RIPK1 inhibitors that additionally possess radical-trapping antioxidant activity. The objective of this review is also to stimulate translational research on complex diseases using polypharmacological drugs acting as necrosis inhibitors.
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BibTeX
@article{delehouze2026necroferrins,
title = {{NecroFerrins as dual therapeutic inhibitors targeting necroptosis and ferroptosis}},
author = {Claire Delehouzé and Stéphane Bach},
journal = {Ferroptosis and Oxidative Stress},
year = {2026},
month = aug,
doi = {10.70401/fos.2026.0041},
url = {https://hal.science/hal-05783170v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - NecroFerrins as dual therapeutic inhibitors targeting necroptosis and ferroptosis
AU - Claire Delehouzé
AU - Stéphane Bach
PY - 2026
DA - 2026/08/05
JO - Ferroptosis and Oxidative Stress
DO - 10.70401/fos.2026.0041
UR - https://hal.science/hal-05783170v1
AB - Over the past two decades, increasing attention has been devoted to regulated forms of cell death that occur independently of apoptosis. Among these, necroptosis and ferroptosis exhibit a necrotic-like morphology, yet are defined by distinct molecular and biochemical signatures. Both pathways have attracted considerable interest due to growing evidence implicating them in the pathogenesis of a wide range of acute and chronic disorders. Notably, the simultaneous engagement of multiple regulated necrosis pathways has been reported in many disease contexts, highlighting the limitations of single-target therapeutic approaches. In this light, the design of multi-target-directed ligands, that is, embracing a polypharmacological strategy, has emerged as a promising direction for the development of future therapies. In this review, we propose the concept of NecroFerrins, a class of small molecules that simultaneously inhibit necroptosis and ferroptosis. Within this class, we identify RIPROStatins as a distinct subclass of RIPK1 inhibitors that additionally possess radical-trapping antioxidant activity. The objective of this review is also to stimulate translational research on complex diseases using polypharmacological drugs acting as necrosis inhibitors.
SN - 3106-8626
SN - 3106-8626
ER -