19545-26-7 Usage
Description
Wortmannin is a potent and selective inhibitor of PI3-kinase, a steroidal metabolite belonging to the viridin group, isolated from Penicillium wortmannii. It exhibits broad-spectrum antifungal, antitumor, and anti-inflammatory activity. Wortmannin is useful for probing PI3-K-mediated cellular events and acts via covalent modification of Lys-802. It is a white to pale yellow powder.
Uses
Used in Cell Biology Research:
Wortmannin is used as an inhibitor of phosphatidylinositol 3-kinase, serving as a cell biology reagent for research purposes. It has been used to inhibit DNA repair, receptor-mediated endocytosis, and cell proliferation. It also inhibits fMLP-induced PIP3 and superoxide anion production in guinea pig neutrophils and blocks insulin metabolic effects in rat adipocytes without affecting the insulin receptor tyrosine kinase activity.
Used in Stem Cell Selection and Differentiation:
Wortmannin acts as an endoderm-inducing agent in stem cell selection and differentiation, playing a crucial role in guiding stem cell fate.
Used as an Autophagy Inhibitor:
Wortmannin is used to inhibit autophagy, a process of self-eating by cells, which can be important in understanding and treating various diseases.
Used in the Pharmaceutical Industry:
Wortmannin is used as an antifungal, antitumor, and anti-inflammatory agent due to its broad-spectrum activity, making it a valuable compound in drug development and therapeutic applications.
Biological Activity
Potent, selective, cell-permeable and irreversible inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase) (IC 50 = 2-4 nM). Also potently inhibits polo-like kinase 1 (PLK1) (IC 50 = 5.8 nM).
Biochem/physiol Actions
Wortmannin is a low molecular weight; hydrophobic fungal metabolite with a sterol-like structure produced by Penicilium fumiculosum. Inhibition of PI3K/Akt signal transduction cascade by wortmannin, enhances the apoptotic effects of radiation or serum withdrawal and blocks the antiapoptotic effect of cytokines. PI3K inhibition by wortmannin also blocks many of the short-term metabolic effects induced by insulin receptor activation. Research has demonstrated that wortmannin inhibits two enzymes from mitotical division, key regulators Polo-like kinase (Plk) family, Plk1 and Plk3.
References
1) Holleran et al. (2003), Use of high-performance liquid chromatography to characterize the rapid decomposition of wortmannin in tissue culture media; Anal. Biochem., 323 19
2) Wymann et al. (1996), Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction; Mol. Cell. Biol., 16 1722
3) Blommaart et al. (1997), The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes; Eur. J. Biochem., 243 240
4) Tomiyama et al. (1995), Wortmannin, a specific phosphatidylinositol 3-kinase inhibitor, inhibits adipocytic differentiation of 3T3-L1 cells; Biochem. Biophys. Res. Commun., 212 263
5) Ui et al. (1995), Wortmannin as a unique probe from an intracellular signaling protein, phosphoinositide 3-kinase; Trends Biochem. Sci., 20 303
Check Digit Verification of cas no
The CAS Registry Mumber 19545-26-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,9,5,4 and 5 respectively; the second part has 2 digits, 2 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 19545-26:
(7*1)+(6*9)+(5*5)+(4*4)+(3*5)+(2*2)+(1*6)=127
127 % 10 = 7
So 19545-26-7 is a valid CAS Registry Number.
InChI:InChI=1/C23H24O8/c1-10(24)30-13-7-22(2)12(5-6-14(22)25)16-18(13)23(3)15(9-28-4)31-21(27)11-8-29-20(17(11)23)19(16)26/h8,12-13,15H,5-7,9H2,1-4H3/t12-,13+,15+,22-,23-/m1/s1
19545-26-7Relevant articles and documents
Wortmannin-C20 conjugates generate wortmannin
Yuan, Hushan,Luo, Ji,Weissleder, Ralph,Cantley, Lewis,Josephson, Lee
, p. 740 - 747 (2006)
We report on C20-6-(N-methylamino)hexanoic conjugates of wortmannin featuring a tertiary enamine attached to the C20 that inhibit phosphoinositol-3-OH kinase (PI3K) by producing wortmannin (Wm) through an intramolecular attack. The generation of Wm by these conjugates permits the design of Wm based PI3K inhibitors that need not fit into the ATP pocket of PI3K, including Wm conjugates of BSA, IgG, or beads. Wm generating WmC20-N(Me)-hexanoate conjugates offer an approach to the design of targeted or slow release forms of Wm which may inhibit PI3K in tissues more selectively than the parent Wm, a compound which has desirable anti-inflammatory and anti-proliferative activities but which also has a variety of toxic effects.
INHIBITION OF PHOSPHATIDYLINOSITOL 3-KINASE WITH 17 beta-HYDROXYWORTMANNIN AND ANALOGS THEREOF
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, (2008/06/13)
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Methods of inhibiting vascular restenosis
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, (2008/06/13)
Wortmannin and certain of its analogs are inhibitors of restinosis.