Deferasirox

Deferasirox is an orally bioavailable synthetic, tridentate iron chelator that binds iron at a 2:1 ratio.¹ It is selective for iron (Fe(III)) over Cu(II), Zn(II), Mg(II), and Ca(II) but does bind to Al(III). Deferasirox decreases iron levels in iron-loaded rat heart cells in vitro by 45.8 and 55.6% compared to control levels when used at concentrations of 160 and 320 µM, respectively.² In hypertransfused rats, deferasirox (200 mg/kg) decreases radiolabeled liver iron levels from 41 to 21.7% and blood iron levels from 8.2 to 3.4%.² It is primarily excreted via the fecal route, in contrast to the iron chelator deferoxamine (Item No. 14595).² Deferasirox also inhibits proliferation of SAS human oral squamous carcinoma cells (EC₅₀ = 21 µM), decreases cyclin D1 protein levels, and increases protein levels of N-Myc downregulated gene 1 (NDRG1) and NDRG3.³ It acts in a synergistic manner when used in combination with gemcitabine (Item Nos. 11690 | 9003096) to reduce proliferation of BxPC-3 pancreatic cancer cells in vitro and reduce tumor growth in a BxPC-3 mouse xenograft model when administered at a dose of 200 mg/kg.⁴ Formulations containing deferasirox have been used in the treatment of β-thalassemia and chronic iron overload.

WARNING This product is not for human or veterinary use.

1. Heinz, U., Hegetschweiler, K., Acklin, P., et al. 4‐[3,5‐bis(2‐hydroxyphenyl)‐1,2,4‐triazol‐1‐yl]‐ benzoic acid: A novel efficient and selective iron(III) complexing agent. Angew. Chem. Int. Ed. 38(17), 2568-2570 (1999).

2. Hershko, C., Konijn, A.M., Nick, H.P., et al. ICL670A: A new synthetic oral chelator: Evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture. Blood 97(4), 1115-1122 (2001).

3. Lee, J.-C., Chiang, K.-C., Feng, T.-H., et al. The iron chelator, Dp44mT, effectively inhibits human oral squamous cell carcinoma cell growth in vitro and in vivo. Int. J. Mol. Sci. 17(9), pii: E1435 (2016).

4. Shinoda, S., Kaino, S., Amano, S., et al. Deferasirox, an oral iron chelator, with gemcitabine synergistically inhibits pancreatic cancer cell growth in vitro and in vivo. Oncotarget 9(47), 28434-28444 (2018).

Hu, S., Sechi, M., Singh, P.K., et al. A novel redox modulator induces a GPX4-mediated cell death that is dependent on iron and reactive oxygen species. J. Med. Chem. 63(17), 9838-9855 (2020).