Deferasirox

Deferasirox is an orally bioavailable synthetic, tridentate iron chelator that binds iron at a 2:1 ratio.{36858} 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.{27434} 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%.{27434} It is primarily excreted via the fecal route, in contrast to the iron chelator deferoxamine (Item No. 14595).{27434} 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.{38960} 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.{36859} Formulations containing deferasirox have been used in the treatment of ?-thalassemia and chronic iron overload.