Wortmannin

Wortmannin

Wortmannin is a steroid metabolite of Penicillium funiculosum and Talaromyces wortmannii, and is a potent and irreversible inhibitor of phosphoinositide 3-kinases (PI3Ks). It was first isolated in 1957 by scientists from the culture broth of Penicillium wortmannin.

Chemistry

Wortmannin is a furanosteroid with a highly oxygenated bicyclic [4.3.1] decane core structure. The molecule also contains a rare 6,7-dihydroxy-3-ene-2-one moiety and a unique 2,3-dihydro-7-hydroxy-2-methyl-5H-furo[3,2-g]chromen-5-one system.

Biological Activity

Wortmannin is a potent and selective inhibitor of PI3Ks. It acts by covalently modifying a conserved lysine residue in the ATP-binding pocket of the enzyme, thereby preventing ATP from binding and the enzyme from functioning. This inhibition of PI3Ks by wortmannin has been shown to have significant effects on a variety of cellular processes, including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking.

Medical Use

Due to its ability to inhibit PI3Ks, wortmannin has been investigated for potential use in the treatment of cancer. However, its clinical development has been hampered by its poor solubility, instability, and toxicity. Despite these challenges, wortmannin and its derivatives continue to be valuable tools for studying the role of PI3Ks in cellular processes and disease.

See Also

• Phosphoinositide 3-kinases
• Penicillium funiculosum
• Talaromyces wortmannii