PEGylated derivatives of cystamine as enhanced treatments for nephropathic cystinosis

详细信息    查看全文

• 作者：Ziad Omran ; Graeme Kay ; Alberto Di Salvo ; Rachel M. Knott ; Donald Cairns
• 关键词：Cystinosis ; Cysteamine ; Cystamine ; Pro-drugs ; PEGylation
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：1 January 2011
• 年：2011
• 卷：21
• 期：1
• 页码：45-47
• 全文大小：285 K

文摘

The genetic disease, nephropathic cystinosis is characterized by lysosomal accumulation of the amino acid cystine. Crystallization of cystine in affected organs, if untreated, results in mortality of the affected individuals by their middle to late teens. The only approved treatment for cystinosis is administration of cysteamine. However, cysteamine is associated with an offending odor and taste and this, coupled to a rapid first pass metabolism and a 6 h dosing regimen, suggest a clear need to improve the therapy. A number of PEGylated derivatives of cystamine, the disulfide counterpart of cysteamine, have been synthesised and evaluated in cultured cystinotic fibroblasts for toxicity and efficacy. All of the tested compounds were non-cytotoxic and displayed a remarkable depletion of intralysosomal cystine.