Identification of KW-2449 as a dual inhibitor of ferroptosis and necroptosis reveals that autophagy is a targetable pathway for necroptosis inhibitors to prevent ferroptosis.

ABSTRACT: Necroptosis and ferroptosis are two distinct forms of necrotic-like cell death in terms of their morphological features and regulatory mechanisms. These two types of cell death can coexist in disease and contribute to pathological processes. Inhibition of both necroptosis and ferroptosis has been shown to enhance therapeutic effects in treating complex necrosis-related diseases. However, targeting both necroptosis and ferroptosis by a single compound can be challenging, as these two forms of cell death involve distinct molecular pathways. In this study, we discovered that KW-2449, a previously described necroptosis inhibitor, also prevented ferroptosis both in vitro and in vivo. Mechanistically, KW-2449 inhibited ferroptosis by targeting the autophagy pathway. We further identified that KW

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC11493980 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature