Wortmannin

Toxicity: Harmful (C)

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

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

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.