|Presentation||1mg of lyophilized powder packaged under inert gas. White to off-white powder.|
|Application||The Wortmannin, (PI3 Kinase inhibitor) controls the biological activity of PI3 Kinase. This small molecule/inhibitor is primarily used for Biochemicals applications.|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Protect from light. Stable for 2 years as supplied at -20°C. Following reconstitution aliquot and store at -20°. The DMSO/ethanol stock solutions are stable for 1-3 months at -20°C.|
|Material Size||1 mg|
|Wortmannin (PI3 Kinase inhibitor) - 2153577||2153577|
|Wortmannin (PI3 Kinase inhibitor) - 2375500||2375500|
|Wortmannin (PI3 Kinase inhibitor)||2930507|
|Wortmannin (PI3 Kinase inhibitor)||3098899|
|Wortmannin (PI3 Kinase inhibitor)||2475643|
|Wortmannin (PI3 Kinase inhibitor)||2960506|
|Wortmannin (PI3 Kinase inhibitor)||2886360|
|Wortmannin (PI3 Kinase inhibitor) - 2202511||2202511|
|Wortmannin (PI3 Kinase inhibitor) - 2290358||2290358|
|Wortmannin (PI3 Kinase inhibitor) - 2558391||2558391|
|Reference overview||Application||Pub Med ID|
|Akt/protein kinase B isoforms are differentially regulated by epidermal growth factor stimulation|
Okano, J., et al
J Biol Chem, 275:30934-42 (2000) 2000
|Wortmannin and its structural analogue demethoxyviridin inhibit stimulated phospholipase A2 activity in Swiss 3T3 cells. Wortmannin is not a specific inhibitor of phosphatidylinositol 3-kinase.|
Cross, M J, et al.
J. Biol. Chem., 270: 25352-5 (1995) 1995
Wortmannin and its structural analogue demethoxyviridin (DMV) have been reported to be specific inhibitors of phosphatidylinositol 3-kinase activity. Here we report that these compounds are not as selective as assumed and demonstrate inhibition of bombesin-stimulated phospholipase A2 activity by both wortmannin and DMV with an IC50 (2 nM) which is slightly more potent than the inhibition of insulin-stimulated phosphatidylinositol 3,4,5-trisphosphate generation in these cells (approximately 10nM). While it has not been possible to fully block in vitro phospholipase A2 activity with wortmannin, inhibition cannot be a consequence of inhibition of PI 3-kinase activity since bombesin fails to generate 3-phosphorylated lipids in the intact cell. Therefore, while wortmannin is indeed a PI 3-kinase inhibitor, it is not as specific as previously reported, and experimental conclusions based solely on its use should be treated with caution.
|Wortmannin as a unique probe for an intracellular signalling protein, phosphoinositide 3-kinase.|
Ui, M, et al.
Trends Biochem. Sci., 20: 303-7 (1995) 1995
Wortmannin is a fungal metabolite that so far has been shown to act as a selective inhibitor of phosphoinositide 3-kinase. It can therefore be used to investigate the convergence between two major cellular signalling systems: those involving G-protein-coupled receptors and those involving receptor tyrosine kinases. Importantly, wortmannin can enter intact cells, making whole-cell studies of the above signalling pathways possible.
|Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption.|
Nakamura, I, et al.
FEBS Lett., 361: 79-84 (1995) 1995
The biological role of phosphatidylinositol (PI)-3 kinase was examined in osteoclast-like multinucleated cells (OCLs) formed in co-cultures of mouse osteoblastic cells and bone marrow cells. The expression of PI-3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin (WT), a specific inhibitor of PI-3 kinase, inhibited PI-3 kinase activity in OCLs both in vitro and in vivo. WT also inhibited pit-forming activity on dentine slices and disrupted a ringed structure of F-actin-containing dots (an actin ring) in OCLs in a dose-dependent manner. The inhibitory profiles of WT for pit and actin ring formation were similar to that for PI-3 kinase activity in OCLs. Electron microscopic analysis revealed that OCLs treated with WT did not form ruffled borders. Instead, numerous electron lucent vacuoles of differing sizes were found throughout the cytoplasm. These results suggest that PI-3 kinase is important in osteoclastic bone resorption.
|Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin|
Okada, T, et al
J Biol Chem, 269:3568-73 (1994) 1994
|Platelet-derived growth factor-induced phosphatidylinositol 3-kinase activation mediates actin rearrangements in fibroblasts.|
Wymann, M and Arcaro, A
Biochem. J., 298 Pt 3: 517-20 (1994) 1994
Various agonist-induced cell responses in neutrophils and fibroblasts, such as chemotaxis and cytoskeletal rearrangements, have been shown to correlate with the synthesis of PtdIns(3,4,5)P3; however, the significance of this rise in second messenger levels is not clear. We show here that wortmannin inhibits platelet-derived growth factor (PDGF)-mediated production of PtdIns(3,4,5)P3 in human foreskin fibroblasts with an IC50 of about 5 nM. A similar inhibition was observed in in vitro assays (IC50 approximately 1 nM) with phosphatidylinositol 3-kinase immunoprecipitated by antibodies directed against the 85 kDa subunit (p85). On the other hand, wortmannin did not affect PDGF-mediated phosphorylation of p85 as detected by immunoprecipitation with anti-phosphotyrosine antibodies, and did not dissociate the complex of p85 and the catalytic subunit (p110) of phosphatidylinositol 3-kinase. These results are consistent with a direct, specific inhibition of the enzyme by wortmannin at concentrations relevant for its previously reported effects on cellular responses. When stimulated with PDGF, human foreskin fibroblasts form circular structures of filamentous actin. Preincubation of these cells with wortmannin inhibits PDGF-mediated actin rearrangements, suggesting a need for PtdIns(3,4,5)P3 formation as a signal for this cell response.
|Wortmannin inhibits mitogen-activated protein kinase activation induced by platelet-activating factor in guinea pig neutrophils.|
Ferby, I M, et al.
J. Biol. Chem., 269: 30485-8 (1994) 1994
Stimulation of guinea pig neutrophils with platelet-activating factor (PAF) caused a rapid and transient activation of mitogen-activated protein kinase (MAPK). Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, partially (approximately 50%) inhibited PAF-induced MAPK activation. Half-maximal inhibition was observed with 200-300 nM wortmannin, while it did not inhibit phorbol ester-induced MAPK activation. Neutrophils preloaded with 1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM) failed to raise cytosolic Ca2+ concentrations toward PAF, while they still responded to PAF with a 40-50% activation of MAPK. However, when cells were treated with BAPTA/AM and wortmannin in combination, the MAPK activation was completely inhibited. These results suggest that PAF activates MAPK through two distinct pathways in guinea pig neutrophils, one Ca(2+)-dependent, and the other Ca(2+)-independent but wortmannin-sensitive.
|Unlocking the Mystery of Cancer: Do the Mutant p110α Subunits of PI3-Kinase Hold the Key?|