期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 52, 期 19, 页码 6163-6167出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm901098m
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资金
- German Academic Exchange Service (DAAD)
- NIH [CA127622]
The natural proteasome inhibitor salinosporamide A from the marine bacterium Salinispora tropica is a promising drug candidate for the treatment of multiple myeloma and mantle cell lymphoma. Using a comprehensive approach that combined chemical synthesis with metabolic engineering, we generated a series of salinosporamide analogues with altered proteasome binding affinity. One of the engineered compounds is equipotent to salinosporamide A in inhibition of the chymotrypsin-like activity of. the proteasome yet exhibits superior activity in the cell-based HCT-116 assay.
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