The less active enantiomer of (–)-nutlin-3
Nutlin-3b is an inactive enantiomer of nutlin-3 [1].
Nutlin-3 is a small-molecule inhibitor of MDM2, interfering with MDM2-directedTP53 degradation. The stabilization of WT-TP53 leads to cell cycle arrest, growth inhibition, and apoptosis. As an inactive enantiomer, Nutlin-3b does not show any effect on the proliferation and has no insignificant effect on gene expression in cancer cells. Nutlin-3b binds MDM2 with about 200-fold lower affinity and is 150 times less active than 3a (an active enantiomer of nutlin-3). Nutlin-3b is usually used as a negative control. It shows no induction of MDM2, p53 or p21 expression and has no ability in colony-formation in H460 cell line. It also has no effect on cell cycle [1, 2].
参考文献:
[1] Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, Myklebost O, Heimbrook DC, Vassilev LT. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93.
[2] Cao C, Shinohara ET, Subhawong TK, Geng L, Kim KW, Albert JM, Hallahan DE, Lu B. Radiosensitization of lung cancer by nutlin, an inhibitor of murine double minute 2. Mol Cancer Ther. 2006 Feb;5(2):411-7.
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