icFSP1

icFSP1 is a potent and selective small molecule inhibitor of human ferroptosis suppressor protein-1 (hFSP1), discovered by a research team at Helmholtz Munich and published in *Nature* in 2023. Unlike earlier FSP1 inhibitors such as iFSP1, which directly block enzymatic activity, icFSP1 operates through a unique mechanism by triggering the subcellular relocalization of FSP1 from the plasma membrane to the cytoplasm. This process induces the formation of FSP1 condensates through phase separation, effectively depleting the protein from its functional site at the membrane and sensitizing cancer cells to ferroptosis—an iron-dependent form of regulated oxidative cell death. Preclinical studies have demonstrated that icFSP1 exhibits significant antitumor activity in melanoma and lung cancer models, particularly when used synergistically with GPX4 inhibitors. Notably, the compound is specific to the human ortholog of FSP1 and does not inhibit the murine version. icFSP1 is currently utilized as a research tool and has not been approved for clinical use.

Other names

CAS 1115910-36-5CAS1115910-36-5CAS-1115910-36-5