wortmannin

Wortmannin is a steroidal metabolite produced by the fungi Penicillium funiculosum and Talaromyces wortmannii. It is a potent, covalent, and irreversible inhibitor of phosphoinositide 3-kinases (PI3Ks), acting on class I, II, and III PI3K isoforms at nanomolar concentrations. Wortmannin also inhibits other kinases at higher concentrations, including DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated kinase (ATM), myosin light chain kinase (MLCK), ATR kinase, and members of the polo-like kinase family such as PLK1 and PLK3. Its mechanism involves covalent modification of lysine residues in the ATP-binding site of these kinases. Wortmannin has been widely used as a research tool to study cell signaling pathways involving PI3Ks, autophagy inhibition, DNA repair inhibition, cell proliferation suppression, receptor-mediated endocytosis blockade, and induction of apoptosis or cell death in various models. It exhibits antiproliferative activity in vitro but is not approved for clinical use due to instability in biological fluids and toxicity concerns[1][2][3][5][6].

Other names

wartmannin