Nigratine as dual inhibitor of necroptosis and ferroptosis regulated cell death
Claire Delehouzé, Arnaud Comte, Stephen Adonai Leon‐Icaza, Céline Cougoule, M. Hauteville, Peter G. Goekjian, J. Chloë Bulinski, Marie-Thérèse Dimanche-Boitrel, Étienne Meunier, M Rousselot, Stéphane Bach
Abstract
Abstract Nigratine (also known as 6E11), a flavanone derivative of a plant natural product, was characterized as highly specific non-ATP competitive inhibitor of RIPK1 kinase, one of the key components of necroptotic cell death signaling. We show here that nigratine inhibited both necroptosis (induced by Tumor Necrosis Factor-α) and ferroptosis (induced by the small molecules glutamate, erastin, RSL3 or cumene hydroperoxide) with EC 50 in the µM range. Taken together, our data showed that nigratine is a dual inhibitor of necroptosis and ferroptosis cell death pathways. These findings open potential new therapeutic avenues for treating complex necrosis-related diseases.