Design, Synthesis and Initial In Vitro Evaluation of Novel Prodrugs for the Treatment of Cystinosis

R.   J.   Anderson; D.      Cairns; W.   A.   Cardwell; M.      Case; P.   W.   Groundwater; A.   G.   Hall; L.      Hogarth; A.   L.   Jones; O.      Meth-Cohn; P.      Suryadevara

Letters in Drug Design & Discovery

Author(s): R. J. Anderson, D. Cairns, W. A. Cardwell, M. Case, P. W. Groundwater, A. G. Hall, L. Hogarth, A. L. Jones, O. Meth-Cohn and P. Suryadevara

DOI: 10.2174/157018006777574258

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Design, Synthesis and Initial In Vitro Evaluation of Novel Prodrugs for the Treatment of Cystinosis

Page: [336 - 345] Pages: 10

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Abstract

Simple amino acid prodrugs of cysteamine and cystamine were synthesized to overcome the problems of palatability and gastrointestinal irritation, while γ-glutamyl prodrugs were synthesized to target the parent drug to γ-glutamyl transpeptidase (GGT). Preliminary cystine-depleting evaluation in vitro suggests further investigation is warranted. Low toxicity of the prodrugs was observed.

Keywords: Cystinosis, prodrugs, GGT, cysteamine, cystamine

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