期刊
JOURNAL OF ANTIBIOTICS
卷 71, 期 1, 页码 135-138出版社
JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2017.100
关键词
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资金
- Japan Society for the Promotion of Science (JSPS) [16H06574, 15H04703, 17K08650]
- Princess Takamatsu Cancer Research Fund
- Mitsubishi foundation
- Tokyo Biochemical Research Foundation
- Grants-in-Aid for Scientific Research [16K21739, 15K01811, 16K15212, 15H04703, 16H06573, 16H06574, 17K08650] Funding Source: KAKEN
Mitogen-activated protein kinase ( MAPK) pathways that direct cellular responses are involved in various biological processes; the RAS-RAF-MEK-ERK pathway is one of the most important MAPK pathways. It is frequently activated in human malignant tumors such as melanomas, thyroid tumors and colorectal carcinomas. Therefore, targeting this pathway has been considered an attractive strategy for new anticancer drugs. In particular, MEK is a promising target because it is a kinase that directly phosphorylates ERK. We performed a screening to discover new MEK inhibitors, and found a guanine derivative produced by Streptomyces sp. MK63-43F2. This guanine derivative was identified to be 2-amino-4-methoxy-5-cyanopyrrolo[2,3-d] pyrimidine (1) through spectroscopic analysis. Compound 1 inhibited MEK1 kinase activity in an ATP-dependent manner and suppressed the phosphorylation of ERK in cancer cells and cell proliferation. Therefore, 1 might be a potent lead compound for new MEK inhibitors.
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