Diazooxonorleucine
[CAS# 157-03-9]

Identification

• Classification: Biochemical >> Common amino acids and protein drugs
• Name: Diazooxonorleucine
• Synonyms: 6-Diazo-5-oxo-L-norleucine; (2S)-2-amino-6-diazo-5-oxohexanoic acid
• Molecular Formula: C₆H₉N₃O₃
• Molecular Weight: 171.15
• CAS Registry Number: 157-03-9
• EC Number: 621-136-2
• SMILES: C(CC(=O)C=[N+]=[N-])[C@@H](C(=O)O)N

Properties

• Melting point: 145 ºC (Expl.)

Safety Data

• Hazard Symbols: GHS06 Danger
• Hazard Statements: H301-H311-H331
• Precautionary Statements: P261-P262-P264-P270-P271-P280-P301+P316-P302+P352-P304+P340-P316-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	3	H331
Reproductive toxicity	Repr.	2	H361

Discovory and Applicatios

Diazooxonorleucine is a synthetic chemical compound known primarily as an inhibitor of certain enzymes involved in amino acid metabolism, specifically targeting glutamine-utilizing enzymes. Its discovery dates back to research aimed at developing tools to study metabolic pathways and to explore potential therapeutic agents for diseases related to abnormal amino acid metabolism.

The compound contains a diazo group (-N‑N=), which is chemically reactive and contributes to its inhibitory effects. Diazooxonorleucine acts by mimicking natural substrates of glutamine-dependent enzymes, thereby competitively inhibiting their activity. This inhibition disrupts metabolic processes that rely on glutamine, such as nucleotide biosynthesis and energy production, making it valuable for biochemical studies.

In terms of application, diazooxonorleucine has been used extensively in research to probe the role of glutamine metabolism in cell proliferation, especially in cancer cells that often show increased glutamine dependence. By blocking glutamine-utilizing enzymes, it helps clarify the contribution of these metabolic pathways to cell growth and survival.

Additionally, diazooxonorleucine has been investigated for its potential to inhibit tumor growth in experimental models by starving cancer cells of essential metabolic intermediates. While promising in preclinical studies, its clinical application is limited by toxicity and stability concerns inherent to diazo compounds.

Beyond cancer research, diazooxonorleucine is also employed in studying neurological conditions and immune responses where glutamine metabolism plays a critical role. Its ability to selectively inhibit glutamine-dependent enzymes makes it a useful biochemical tool across various fields of biomedical research.

Overall, diazooxonorleucine is a research compound discovered for its ability to inhibit glutamine-utilizing enzymes, facilitating the study of metabolic pathways involved in health and disease. Its primary applications lie in laboratory research, particularly in understanding cancer metabolism and related biological processes.

References

1956. Alterations in Calcium Metabolism in Cancer Patients Treated with 6-Diazo-5-Oxo-L-Norleucine. Proceedings of the Society for Experimental Biology and Medicine, 93(2).
DOI: 10.3181/00379727-93-22741

1959. Potential anti-cancer agents--II. A proposed mechanism for the anti-cancer action of L-azaserine and 6-diazo-5-oxo-L-norleucine. Biochemical Pharmacology, 2(4).
DOI: 10.1016/0006-2952(59)90064-4

2024. Therapeutic resurgence of 6-diazo-5-oxo-L-norleucine (DON) through tissue-targeted prodrugs. Advances in Pharmacology, 100.
DOI: 10.1016/bs.apha.2024.04.003