6-Diazo-5-oxo-L-norleucine

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6-Diazo-5-oxo-L-norleucine

6-Diazo-5-oxo-L-norleucine (DON) is a glutamine antagonist that is used in biological research. It is a derivative of the amino acid norleucine. DON has been studied for its potential use in the treatment of various types of cancer, including leukemia, lymphoma, and solid tumors.

History

DON was first synthesized in the 1950s and has been used in biological research for several decades. It was initially studied for its potential use in the treatment of cancer, but its clinical development was halted due to toxicity concerns. However, recent advances in drug delivery technologies have renewed interest in DON as a potential anti-cancer agent.

Mechanism of Action

DON inhibits the activity of glutaminase, an enzyme that converts glutamine into glutamate. This inhibition disrupts the metabolism of cancer cells, which are often heavily dependent on glutamine for growth and survival. By depriving cancer cells of glutamine, DON can induce cell death and inhibit tumor growth.

Clinical Development

Despite its early promise, the clinical development of DON has been hampered by its toxicity. High doses of the drug can cause severe side effects, including nausea, vomiting, and neurotoxicity. However, recent advances in drug delivery technologies, such as liposomal encapsulation, have made it possible to deliver DON to tumor cells more selectively, potentially reducing its toxicity.

Current Research

Current research on DON is focused on improving its delivery to tumor cells and reducing its toxicity. Several studies are also investigating the combination of DON with other anti-cancer agents to enhance its efficacy. In addition, researchers are studying the molecular mechanisms by which DON induces cell death in cancer cells, with the aim of identifying new targets for cancer therapy.

See Also

• Glutamine
• Glutaminase
• Cancer
• Chemotherapy