发明名称 |
Cobalamin conjugates for anti-tumor therapy |
摘要 |
The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5'-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.
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申请公布号 |
US2005054607(A1) |
申请公布日期 |
2005.03.10 |
申请号 |
US20030659501 |
申请日期 |
2003.09.10 |
申请人 |
WEINSHENKER NED M.;WEST FREDERICK G.;ARANEO BARBARA A.;LI WEIPING |
发明人 |
WEINSHENKER NED M.;WEST FREDERICK G.;ARANEO BARBARA A.;LI WEIPING |
分类号 |
A01N43/04;A61K;A61K31/70;A61K31/714;A61K47/48;(IPC1-7):A61K31/714 |
主分类号 |
A01N43/04 |
代理机构 |
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地址 |
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