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Deferitazole, a new orally active iron chelator

Research output: Contribution to journalArticle

Robert Charles Hider, Xiaole Kong, Vincenzo Abbate, Rachel Harland, Kelly Conlon, Tim Luker

Original languageEnglish
Pages (from-to) 5197-5204
JournalDalton Transactions
Volume44
DOIs
Published17 Feb 2015

King's Authors

Abstract

Following a systematic search of desferrithiocin analogs, a polyether derivative, deferitazole (formerly FBS0701), has entered into phase 1 and 2 clinical trials with promising biological properties. However, until now, detailed physicochemical properties of this chelator have not been reported. The compound displays a high affinity and selectivity for iron(III) as demonstrated by the log β2 = 33.39 ± 0.03 and the pFe3+ value of 22.3. Two equilibrating isomeric forms of the iron(III) complex exist under biological conditions. Deferitazole also binds the trivalent metals AlIII and LaIII with high affinity; log β2 values, 26.68 and 21.55 respectively. The affinity of deferitazole for divalent cations is somewhat lower, with the exception of CuII which possesses a log β2 value of 25.5; deferitazole scavenges iron from labile sources such as citrate and albumin with efficiencies comparable with those of other therapeutic iron chelators, including deferasirox, deferiprone and desferrioxamine. The FeIII(deferitazole)2 is stable under physiological conditions and does not redox cycle. The high affinity of deferitazole for iron(III) renders it unlikely that this chelator will lead to the redistribution of iron and consequently deferitazole shows considerable promise as a therapeutic iron(III) chelator.

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