产品号 #73562_C
PI3K/AKT通路抑制剂；抑制PI3K和PLK
总览
Wortmannin（渥曼青霉素）是一种真菌代谢物，可与I、II和III类磷脂酰肌醇-3-激酶（PI3K）共价结合并抑制其活性。II类PI3K的物种特异性差异决定了其对果蝇、小鼠和人的IC₅₀值分别为5、50和450 nM（Fruman et al.; Wymann et al.; Okada et al.）。渥曼青霉素还能抑制polo样激酶（PLK）PLK1和PLK3，IC₅₀值分别为24和49 nM（Liu et al. 2005; Liu et al. 2007）。在高浓度下，它还可以抑制其他激酶，例如哺乳动物雷帕霉素靶蛋白（mTOR）、DNA依赖性蛋白激酶催化亚基（DNA-PKcs）、磷脂酰肌醇-4-激酶（PI4K）、肌球蛋白轻链激酶（MLCK）和丝裂原活化蛋白激酶（MAPK）（Fruman et al.; Meyers & Cantley; Hartley et al.; Brunn et al.; Nakanishi et al.）。
癌症研究
·在体外对多种人肿瘤细胞系表现出细胞毒活性，并在小鼠C3H乳腺癌和BxPC-3胰腺癌细胞异种移植中表现出抗肿瘤活性（Schultz et al.; Yuan et al.）。
细胞类型
癌细胞及细胞系
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
研究领域
癌症
CAS 编号
19545-26-7
化学式
C₂₃H₂₄O₈
纯度
≥98%
通路
PI3K/AKT，PLK
靶点
PI3K，PLK
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Educational Materials (2)
Publications (11)
Covalent reactions of wortmannin under physiological conditions. Chemistry & biology 2007
Abstract
Wortmannin (Wm), a steroid-like molecule of 428.4 Da, appears to be unstable in biological fluids (apparent chemical instability), yet it exhibits an antiproliferative activity in assays employing a 48 hr incubation period (prolonged bioactivity), a situation we refer to as the wortmannin paradox." Under physiological conditions�
Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. The Journal of biological chemistry 2007
Abstract
Polo-like kinases play crucial roles throughout mitosis. We previously reported that wortmannin potently inhibits Polo-like kinase 1 (Plk1). In this study, we show that wortmannin also strongly inhibits Polo-like kinase 3 (Plk3). To further characterize this inhibition, we identified the sites of labeling on Plk1 and Plk3 targeted by AX7503, a tetramethylrhodamine-wortmannin conjugate. AX7503 labeling on Plk1 and Plk3 was found to occur on a conserved ATP binding site residue. In addition, we show that wortmannin inhibits Plk3 activity in live cells at concentrations commonly used to inhibit the more well known targets of wortmannin, the phosphoinositide 3-kinases. Importantly, we found that inhibition of Plk3 by wortmannin lead to a decrease in phosphorylation of p53 on serine 20 induced by DNA damage, demonstrating the effect of wortmannin on a downstream Plk3 target. Taken together, our results suggest that wortmannin can affect multiple functions of Plk3 in cell cycle progression and at the DNA damage check point. The identification of the labeling sites of Plk1 and Plk3 by AX7503 may be useful in designing more effective compounds to target Polo-like kinases for cancer treatment and also may be useful for the structural study of Plk domains.
Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Chemistry & biology 2005
Abstract
Polo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetramethylrhodamine-wortmannin conjugate (AX7503) that permits rapid detection of PLK1 activity and expression in complex proteomes. Importantly, we show that wortmannin inhibits PLK1 activity in an in vitro kinase assay with an IC(50) of 24 nM and when incubated with intact cells. Taken together, our results indicate that, at the concentrations of wortmannin commonly used to inhibit PI 3-kinases, PLK1 is also significantly inhibited.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 19545-26-7 |
| Chemical Formula | C₂₃H₂₄O₈ |
| Purity | ≥ 98% |
| Target | PI3K, PLK |
| Pathway | PI3K/AKT, PLK |
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