SFXN5 Inhibitors

Chemical inhibitors of SFXN5 can impede its function in several ways, primarily by disrupting the mitochondrial environment or the iron transport pathways that are crucial for its activity. Antimycin A, Oligomycin, Thenoyltrifluoroacetone (TTFA), and Rotenone are inhibitors that target different complexes of the mitochondrial electron transport chain. Antimycin A, by inhibiting complex III, disrupts the mitochondrial membrane potential, which is necessary for SFXN5's role in mitochondrial iron transport. Oligomycin blocks ATP synthase, thereby diminishing the energy supply required for SFXN5's function. TTFA, as a complex II inhibitor, and Rotenone, a complex I inhibitor, contribute to the reduction of mitochondrial function, which can lead to an indirect decrease in SFXN5 activity, due to its association with mitochondrial metabolism.

Deferoxamine, Ciclopirox, and Tetrathiomolybdate are iron chelators that sequester iron, thereby limiting its availability for transport by SFXN5. Deferoxamine and Tetrathiomolybdate, by reducing free iron levels, can inhibit the iron transport function of SFXN5 within mitochondria. Ciclopirox also has similar iron-chelating effects, which can lead to an indirect inhibition of SFXN5. Additionally, Mitoquinone mesylate, by modulating mitochondrial oxidative stress, can alter the redox state within mitochondria and can thus affect the functioning of SFXN5 related to iron handling. Iodoacetate, by interfering with glycolysis, can lead to a decrease in ATP levels, which is necessary for SFXN5's energy-dependent iron transport. Auranofin, by inhibiting thioredoxin reductase, alters cellular redox homeostasis, which can indirectly affect SFXN5's mitochondrial function. Lastly, inhibitors like KCN and Sodium azide directly inhibit mitochondrial complex IV, leading to a cessation of electron transport and a subsequent decrease in ATP production, which can result in an inhibition of SFXN5's role in iron metabolism.