Wortmannin

Wortmannin is a fungal metabolite known for its potent and selective inhibitory effects onphosphatidylinositol 3-kinase (PI 3-kinase). It serves as a cell-permeable and irreversible inhibitor, demonstrating an IC50 of 5 nM in both purified preparations and cytosolic fractions. When fibroblasts are preincubated with wortmannin, it effectively abolishes the formation of Ins (3,4,5) P3 mediated byplatelet-derived growth factor (PDGF). Wortmannin blocks the catalytic activity of PI 3-kinase without interfering with upstream signaling events, making it a valuable tool for studying PI 3-kinase pathways. Additionally, it inhibits the metabolic effects of insulin in isolated rat adipocytes without affecting the insulin receptor′s tyrosinekinase activity. Wortmannin inhibits MAP kinase activation induced by platelet-activating factor in guinea pig neutrophils at concentrations ranging from 0.2 to 0.3 µM. It also demonstrates the ability to inhibit osteoclastic bone resorption. While it primarily targets PI 3-kinase, wortmannin can inhibit other kinases, such as myosin light chain kinase, with an IC50 of 200 nM, and PI 4-kinase at concentrations 100-fold higher than those required for PI3-kinase inhibition. Wortmannin also blocks phospholipase D activity. This steroid metabolite can inhibit human non-small cell lung cancer (NSCLC) both in vitro and in vivo. It acts as an effective radio sensitizer, increasing the sensitivity of NSCLC cells to ionizing radiation.

Wortmannin has been used:

• to treat the cells transfected withspecific vectors to investigate its role as an autophagy inhibitor
• as a classical autophagy inhibitor to evaluate its effects on autophagic flux in non-small cell lung cancer (NSCLC) cells, specifically H460 cells
• in inhibitor treatment experiments to inhibit autophagy and also used along with bafilomycin A1 to inhibit lysosomal degradation

Packaged under inert gas

A 10 mM (1 mg/233 µl) solution of Wortmannin (Cat. No. 681675) in DMSO.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Harmful (C)