Pyridoxal isonicotinoyl hydrazone

Pyridoxal isonicotinoyl hydrazone is an orally active and lipophilic iron-specific chelator that acts as a non-competitive inhibitor of ferrochelatase (FECH) by binding iron ions. Pyridoxal isonicotinoyl hydrazone disrupts heme biosynthesis, leading to reduced FECH stability and increased protoporphyrin IX (PPIX) accumulation. Pyridoxal isonicotinoyl hydrazone is promising for research of iron-overload diseases (e.g., β-thalassemia)^{[1][2][3][4][5][6]}. In Vitro:Pyridoxal isonicotinoyl hydrazone (50-800 µM; 24-72 h) decreases FECH protein levels without affecting FECH mRNA, accompanied by increased ALAS1 protein at high doses in primary human hepatocytes (PHHs) and HepG2/C3A cells^[3].
Pyridoxal isonicotinoyl hydrazone (50 µM; 24 h) reduces FECH protein by 40%, an effect reversed by iron supplementation in HepG2/C3A cells^[3].
In Vivo:Pyridoxal isonicotinoyl hydrazone (100-800 mg/kg; oral gavage, daily for 90 days) causes dose-dependent hepatic degeneration, increased serum transaminases, and vascular congestion in kidneys/spleens in Wistar rats ^[4].