Wortmannin

PI3K/AKT pathway inhibitor; Inhibits PI3K and PLKs

Wortmannin

PI3K/AKT pathway inhibitor; Inhibits PI3K and PLKs

From: 83 USD
Catalog #
73562_C
PI3K/AKT pathway inhibitor; Inhibits PI3K and PLKs

Overview

Wortmannin is a fungal metabolite that covalently binds to and inhibits phosphatidylinositol-3-kinases (PI3K) of class I, II, and III. Species-specific differences in the class II PI3Ks determine sensitivity with IC₅₀ = 5, 50, and 450 nM for Drosophila, mouse, and human, respectively (Fruman et al.; Wymann et al.; Okada et al.). Wortmannin also inhibits polo-like kinases (PLK) PLK1 and PLK3 with IC₅₀ = 24 and 49 nM, respectively (Liu et al. 2005; Liu et al. 2007). At high concentrations it can also inhibit other kinases such as mammalian target of rapamycin (mTOR), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), phosphatidylinositol-4-kinase (PI4K), myosin light-chain kinase (MLCK), and mitogen-activated protein kinase (MAPK; Fruman et al.; Meyers & Cantley; Hartley et al.; Brunn et al.; Nakanishi et al.).

CANCER RESEARCH
· Exhibits cytotoxic activity on a number of human tumor cell lines in vitro, and anti-tumor activity in mouse xenografts of C3H mammary carcinoma and BxPC-3 pancreatic carcinoma cells (Schultz et al.; Yuan et al.).
Alternative Names
KY 12420
Cell Type
Cancer Cells and Cell Lines
Species
Human, Mouse, Rat, Non-Human Primate, Other
Area of Interest
Cancer
CAS Number
19545-26-7
Chemical Formula
C₂₃H₂₄O₈
Molecular Weight
428.4 g/mol
Purity
≥ 98%
Pathway
PI3K/AKT, PLK
Target
PI3K, PLK

Scientific Resources

Product Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
Wortmannin
Catalog #
73562, 73564
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
Wortmannin
Catalog #
73562, 73564
Lot #
All
Language
English

Educational Materials (2)

Data and Publications

Publications (11)

Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. Liu Y et al. 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.
Covalent reactions of wortmannin under physiological conditions. Yuan H et al. 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�
Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Liu Y et al. 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.

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