| Revision as of 21:44, 17 October 2011 editThe chemistds (talk | contribs)Extended confirmed users5,761 edits added CSID, (Std)InChI & (Std)InChIKey← Previous edit |
Latest revision as of 15:18, 20 May 2024 edit undoUhooep (talk | contribs)Extended confirmed users30,796 editsm wl |
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{{Short description|Chemical compound}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 412635297 |
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| verifiedrevid = 456079677 |
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| IUPAC_name = ''O''-(2-Diazoacetyl)-L-serine |
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| IUPAC_name = ''O''-(2-Diazoacetyl)-L-serine |
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| image = azaserine.png |
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| image = Azaserine.svg |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = |
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| routes_of_administration = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| metabolism = |
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| metabolism = |
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| elimination_half-life = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 115-02-6 |
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| CAS_number = 115-02-6 |
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| ATC_prefix = none |
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| ATC_prefix = none |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| DrugBank = |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 87299V3Q9W |
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| UNII = 87299V3Q9W |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D03032 |
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| KEGG = D03032 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 74846 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 1095699 |
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| ChEMBL = 1095699 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 16735688 |
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| ChemSpiderID = 16735688 |
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| SMILES = O=C(OC(N)C(O)=O)/C== |
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| smiles = O=C(OC(N)C(O)=O)/C== |
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| 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 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| InChIKey = MZZGOOYMKKIOOX-VKHMYHEABI |
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| 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 |
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| 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 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = MZZGOOYMKKIOOX-VKHMYHEASA-N |
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| StdInChIKey = MZZGOOYMKKIOOX-VKHMYHEASA-N |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=5 | H=7 | N=3 | O=4 |
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| C=5 | H=7 | N=3 | O=4 |
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| molecular_weight = 173.127 g/mol |
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'''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. |
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'''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). |
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== Mechanism of Action == |
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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 ]. |
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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 ]. |
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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 ]. |
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== Properties== |
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{{pharma-stub}} |
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Azaserine has a solubility of 50 mg/mL in water, a melting point of 146-162 °C, a vapor pressure of 1.53x10<sup>−10</sup>mmHg at 25 °C, and decomposes before melting.{{cn|date=April 2014}} |
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== References == |
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{{refbegin}} |
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* {{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 }} |
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* {{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 }} |
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* {{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 }} |
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* {{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}} |
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* {{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 }} |
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{{refend}} |
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