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Folate pro-drug of cystamine as an enhanced treatment for nephropathic cystinosis.

Abstract：

:Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised intracellular levels of the amino acid, cystine. If untreated, the disease, progressively deteriorates towards end stage renal disease (ESRD) at the end of the first decade. The disease is caused by a defect in the lysosomal transport mechanism for cystine. The treatment of choice is the aminothiol cysteamine which acts as a lysine mimic. However, cysteamine possesses an offensive taste and smell and irritates the gastrointestinal tract leading to nausea and vomiting following administration. Furthermore, the rapid metabolism of cysteamine requires oral administration every 6 h for life, in consequence, the patient compliance is poor. As part of our continuing work to obtain new pro-drugs for the treatment of this genetic disease, we have synthesised a folate derivative of cystamine, the disulfide derivative of cysteamine. This new pro-drug was non cytotoxic, showed greater ability to deplete intralysosomal cystine than the current treatment, and, in fact has been the most effective reducer of intralysosomal cystine discovered in our laboratories to date.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Omran Z,Kay G,Hector EE,Knott RM,Cairns D

doi

10.1016/j.bmcl.2011.02.048

subject

Has Abstract

pub_date

2011-04-15 00:00:00

pages

2502-4

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00232-0

journal_volume

21

pub_type

杂志文章

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