期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 16, 期 23, 页码 10022-10028出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2008.10.024
关键词
Hdm2; Mdm2; Pyridoacridine; Lissoclinum; Marine natural product; Ascidian
资金
- National Cancer Institute, National Institutes of Health [N01-CO-12400]
Compounds that stabilize p53 could suppress tumors providing a additional tool to fight cancer. Mdm2, and the human ortholog, Hdm2 serve as ubiquitin E3 ligases and target p53 for ubiquitylation and degradation. Inhibition of Hdm2 stabilizes p53, inhibits cell proliferation and induces apoptosis. Using HTS to discover inhibitors, we identified three new alkaloids, isolissoclinotoxin B, diplamine B, and lissoclinidine B from Lissoclinum cf. badium. Lissoclinidine B inhibited ubiquitylation and degradation of p53, and selectively killed transformed cells harboring wild-type p53, suggesting this compound could be used to develop new treatments. (c) 2008 Elsevier Ltd. All rights reserved.
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