Ferritin PROTAC DeFer-2

Ferritin PROTAC DeFer-2 is a proteolysis-targeting chimera (PROTAC) containing oleic acid , which binds to ferritin dimers, conjugated to von Hippel-Lindau ligand , which binds to VHL E3 ligase, via an alkyl linker.¹ It induces ferritin degradation in B16/F10 murine melanoma cells when used at a concentration of 0.5 µM, an effect not induced by a negative control with an inverted VHL ligand 1 stereocenter, indicating that the E3 ligase activity of VHL ligand 1 is required for this effect. Ferritin PROTAC DeFer-2 (5 µM) increases intracellular levels of free iron and induces pyroptosis in B16/F10 cells. Ferritin PROTAC De-Fer-2 (10 mg/kg) encapsulated in albumin nanoparticles reduces tumor growth and increases survival in a B16/F10 murine melanoma model.