期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 34, 页码 12556-12561出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1319488111
关键词
transcriptional control; protein-protein interactions; xenograft; combinatorial library; gene signature
资金
- Pfizer [SPF-1892]
- National Cancer Institute [R01 CA078230]
- Skaggs Institute for Chemical Biology
- Austrian Science Fund [P23652, P22608]
- Austrian Science Fund (FWF) [P 23652, P 22608] Funding Source: researchfish
- Austrian Science Fund (FWF) [P23652, P22608] Funding Source: Austrian Science Fund (FWF)
In a fluorescence polarization screen for the MYC-MAX interaction, we have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Krohnke pyridine library. The K-d of KJ-Pyr-9 for MYC in vitro is 6.5 +/- 1.0 nM, as determined by backscattering interferometry; KJ-Pyr-9 also interferes with MYC-MAX complex formation in the cell, as shown in a protein fragment complementation assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic transformation in cell culture; it has no or only weak effects on the oncogenic activity of several unrelated oncoproteins. KJ-Pyr-9 preferentially interferes with the proliferation of MYC-overexpressing human and avian cells and specifically reduces the MYC-driven transcriptional signature. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells.
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