Ferroportin-1 Activators

The class of chemicals known as Ferroportin-1 activators comprises a diverse set of compounds that modulate the activity of Ferroportin-1, a crucial protein involved in cellular iron homeostasis. These activators exert their effects through intricate signaling pathways, influencing Ferroportin-1 expression and function to regulate the export of iron from cells. Hemin, for instance, activates Ferroportin-1 by upregulating heme oxygenase-1 (HO-1), leading to increased heme degradation. This process results in the liberation of iron, which, in turn, activates Ferroportin-1, facilitating the export of iron from cells and contributing to the delicate balance of cellular iron homeostasis. Diflunisal operates by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1), a key player in cellular signaling. This inhibition enhances Ferroportin-1 expression, allowing for increased iron export and playing a pivotal role in the maintenance of cellular iron homeostasis.

AICAR, a potent activator, stimulates AMP-activated protein kinase (AMPK), suppressing mTORC1 and subsequently activating Ferroportin-1. This AMPK-mediated regulation provides a cellular mechanism for controlling iron export and maintaining iron homeostasis. Deferoxamine, on the other hand, operates through chelation, preventing the intracellular accumulation of iron. By binding to iron, Deferoxamine facilitates Ferroportin-1-mediated iron export, contributing to the prevention of iron-induced cellular damage and highlighting its role in cellular iron homeostasis regulation. Piperlongumine adds another dimension by activating Ferroportin-1 through the induction of reactive oxygen species (ROS)-mediated NRF2 activation. This activation enhances Ferroportin-1 expression, promoting iron export and influencing cellular iron homeostasis through the regulation of NRF2-mediated antioxidant responses. Clioquinol, Salinomycin, 6-AN, Ciclopirox, Masitinib, and Sulforaphane each contribute to the class of Ferroportin-1 activators by targeting specific pathways associated with iron metabolism. Whether through Wnt/β-catenin, JAK2/STAT3, HIF-2α, Lyn kinase, or NRF2-mediated signaling, these chemicals exemplify the diverse strategies employed to modulate Ferroportin-1 activity and maintain the delicate balance of cellular iron homeostasis.