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{{Short description|Chemical compound}}
{{Drugbox {{Drugbox
| Verifiedfields = changed | Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 412635297 | verifiedrevid = 456079677
| IUPAC_name = ''O''-(2-Diazoacetyl)-L-serine | IUPAC_name = ''O''-(2-Diazoacetyl)-L-serine
| image = azaserine.png | image = Azaserine.svg


<!--Clinical data--> <!--Clinical data-->
Line 15: Line 17:
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = | legal_status =
| routes_of_administration = | routes_of_administration =


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
Line 22: Line 24:
| metabolism = | metabolism =
| elimination_half-life = | elimination_half-life =
| excretion = | excretion =


<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 115-02-6 | CAS_number = 115-02-6
| ATC_prefix = none | ATC_prefix = none
Line 31: Line 34:
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = | DrugBank =
| UNII_Ref = {{fdacite|changed|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 87299V3Q9W | UNII = 87299V3Q9W
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03032 | KEGG = D03032
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 74846
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1095699 | ChEMBL = 1095699
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 16735688 | ChemSpiderID = 16735688
| SMILES = O=C(OC(N)C(O)=O)/C== | smiles = O=C(OC(N)C(O)=O)/C==
| InChI = 1/C5H7N3O4/c6-3(5(10)11)2-12-4(9)1-8-7/h1,3H,2,6H2,(H,10,11)/t3-/m0/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
⚫ | InChIKey = MZZGOOYMKKIOOX-VKHMYHEABI
| StdInChI = 1S/C5H7N3O4/c6-3(5(10)11)2-12-4(9)1-8-7/h1,3H,2,6H2,(H,10,11)/t3-/m0/s1 | StdInChI = 1S/C5H7N3O4/c6-3(5(10)11)2-12-4(9)1-8-7/h1,3H,2,6H2,(H,10,11)/t3-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MZZGOOYMKKIOOX-VKHMYHEASA-N
⚫ | StdInChIKey = MZZGOOYMKKIOOX-VKHMYHEASA-N


<!--Chemical data--> <!--Chemical data-->
| C=5 | H=7 | N=3 | O=4 | C=5 | H=7 | N=3 | O=4
| molecular_weight = 173.127 g/mol
}} }}


'''Azaserine''' is a naturally occurring serine derivative diazo compound with ] and ] properties deriving from its action as a ] and structural similarity to ]. Azaserine acts by ] ], a key enzyme responsible for glutamine metabolism.
'''Azaserine''' is a ] primarily used for researching pancreatic cancer in animal models. It is a ] analogue that irreversibly inhibits glutamine utilizing enzymes such as ], which is involved in the biosynthesis of ] (IMP). IMP is an important precursor to the ] ]s which include ] (AMP) and ] (GMP).


== Mechanism of Action ==
Further enzymes of purine and pyrimidine metabolism are inhibited as well. Therefore it was tested as anti-cancer drug by different authors in different indications (not only pancreatic cancer) in pre-clinical settings. Further glutamine analogues that were tested as anti-cancer drugs are ] and ].


Azaserine inhibits the rate limiting step of the metabolic hexosamine pathway and irreversibly inhibits ] 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-], directly reducing the concentration of ].
⚫ ]
]
]


Azaserine also downregulates the expression of ] and ] in response to ], and research indicates that it may have potential in identifying the <small>L</small>-leucine-favoring system transporter in human ].


== Properties==
{{pharma-stub}}
Azaserine has a solubility of 50&nbsp;mg/mL in water, a melting point of 146-162&nbsp;°C, a vapor pressure of 1.53x10<sup>−10</sup>mmHg at 25&nbsp;°C, and decomposes before melting.{{cn|date=April 2014}}

== References ==
{{refbegin}}
* {{cite journal | vauthors = Segel GB, Woodlock TJ, Murant FG, Lichtman MA | title = Photoinhibition of 2-amino-2-carboxybicycloheptane transport by O-diazoacetyl-L-serine. An initial step in identifying the L-system amino acid transporter | journal = The Journal of Biological Chemistry | volume = 264 | issue = 28 | pages = 16399–402 | date = October 1989 | doi = 10.1016/S0021-9258(19)84720-8 | pmid = 2789219 | doi-access = free }}
* {{cite journal | vauthors = Hull RL, Zraika S, Udayasankar J, Kisilevsky R, Szarek WA, Wight TN, ] | title = Inhibition of glycosaminoglycan synthesis and protein glycosylation with WAS-406 and azaserine result in reduced islet amyloid formation in vitro | journal = American Journal of Physiology. Cell Physiology | volume = 293 | issue = 5 | pages = C1586–93 | date = November 2007 | pmid = 17804609 | pmc = 2365901 | doi = 10.1152/ajpcell.00208.2007 }}
* {{cite journal | vauthors = Wada K, Hiratake J, Irie M, Okada T, Yamada C, Kumagai H, Suzuki H, Fukuyama K | title = Crystal structures of Escherichia coli gamma-glutamyltranspeptidase in complex with azaserine and acivicin: novel mechanistic implication for inhibition by glutamine antagonists | journal = Journal of Molecular Biology | volume = 380 | issue = 2 | pages = 361–72 | date = July 2008 | pmid = 18555071 | doi = 10.1016/j.jmb.2008.05.007 }}
* {{cite journal | vauthors = Rajapakse AG, Ming XF, Carvas JM, Yang Z | title = The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 296 | issue = 3 | pages = H815–22 | date = March 2009 | pmid = 19136606 | doi = 10.1152/ajpheart.00756.2008 | url = http://doc.rero.ch/record/12007/files/yang_hbi.pdf}}
* {{cite journal | vauthors = Lebedeva ZI, Kabanova EA, Berezov TT | title = 6-diazo-5-oxo-L-norleucine and azaserine as affinity inhibitors of glutamin(asparagin)ase | journal = Biochemistry International | volume = 12 | issue = 3 | pages = 413–20 | date = March 1986 | pmid = 3707592 }}
{{refend}}

]
⚫ ]

Latest revision as of 15:18, 20 May 2024

Chemical compound Pharmaceutical compound
Azaserine
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • O-(2-Diazoacetyl)-L-serine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.003.692 Edit this at Wikidata
Chemical and physical data
FormulaC5H7N3O4
Molar mass173.128 g·mol
3D model (JSmol)
SMILES
  • O=C(OC(N)C(O)=O)/C==
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
  • Key:MZZGOOYMKKIOOX-VKHMYHEASA-N
  (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. Azaserine 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 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 1.53x10mmHg at 25 °C, and decomposes before melting.

References

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