Azaserine

Azaserine
Clinical data

ATC code	none
Identifiers
IUPAC name O-(2-Diazoacetyl)-L-serine
CAS Number	115-02-6^Y
PubChem (CID)	5284344
ChemSpider	16735688^Y
UNII	87299V3Q9W^Y
KEGG	D03032^Y
ChEBI	CHEBI:74846^N
ChEMBL	CHEMBL1095699^Y
Chemical and physical data
Formula	C₅H₇N₃O₄
Molar mass	173.127 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(OC[C@H](N)C(O)=O)/C=[N+]=[N-]
InChI InChI=1S/C5H7N3O4/c6-3(5(10)11)2-12-4(9)1-8-7/h1,3H,2,6H2,(H,10,11)/t3-/m0/s1^Y Key:MZZGOOYMKKIOOX-VKHMYHEASA-N^Y
^NY (what is this?) (verify)

Azaserine is a naturally occurring serine derivative diazo compound with antineoplastic and antibiotic properties deriving from its action as a purinergic antagonist and structural similarity to glutamine. Azazerine acts by competitively inhibiting glutamine amidotransferase, a key enzyme responsible for glutamine metabolism.

Mechanism of Action

Azaserine inhibits the rate limiting step of the metabolic hexosamine pathway and an irreversibly inhibits γ-glutamyltransferase by acting directly at the substrate-binding pocket. Independent of hexosamine pathway inhibition, azaserine has been demonstrated to protect against hyperglycemic endothelial damage by elevating serum concentrations of manganese-superoxide dismutase, directly reducing the concentration of reactive oxygen species.

Azaserine also downregulates the expression of VCAM-1 and ICAM-1 in response to TNF-α, and research indicates that it may have potential in identifying the L-leucine-favoring system transporter in human T-lymphocytes.

Properties

Azaserine has a solubility of 50 mg/mL in water, a melting point of 146-162 °C, a vapor pressure of 1.53x10⁻¹⁰mmHg at 25 °C, and decomposes before melting.

References

Segel, G.B., et al. 1989. J. Biol. Chem. 264: 16399-16402. PMID 2789219
Hull, R.L., et al. 2007. Am. J. Physiol., Cell Physiol. 293: C1586-C1593. PMID 17804609
Wada, K., et al. 2008. J. Mol. Biol. 380: 361-372. PMID 18555071
Rajapakse, A.G., et al. 2009. Am. J. Physiol. Heart Circ. Physiol. 296: H815-H822. PMID 19136606
Angana Gupta Rajapakse, Xiu-Fen Ming, João M. Carvas, and Zhihong Yang. The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects. http://ajpheart.physiology.org/content/296/3/H815.full
Lebedeva ZI, Kabanova EA, Berezov TT. 1986 Mar;12(3):413-20. 6-diazo-5-oxo-L-norleucine and azaserine as affinity inhibitors of glutamin(asparagin)ase.

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