| Revision as of 20:00, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,074 edits Saving copy of the {{chembox}} taken from revid 452221925 of page Acivicin for the Chem/Drugbox validation project (updated: 'CASNo'). |
Latest revision as of 02:36, 12 July 2024 edit Pbsouthwood (talk | contribs)Administrators151,111 edits Adding short description: "Idinhibitor of gamma-glutamyl transferase.", overriding automatically generated descriptionTag: Shortdesc helper |
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{{Short description|Idinhibitor of gamma-glutamyl transferase.}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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{{chembox |
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{{chembox |
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| verifiedrevid = 450844030 |
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| Watchedfields = changed |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| verifiedrevid = 477240787 |
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| UNII = O0X60K76I6 |
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| ImageFile = Acivicin structure.svg |
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| ImageFile = Acivicin structure.svg |
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| ImageSize = 200px |
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| ImageSize = 200px |
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| IUPACName = (2''S'')-Aminoethanoic acid |
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| IUPACName = (2''S'')-Aminoethanoic acid |
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| OtherNames = Antibiotic AT 125 |
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| OtherNames = Antibiotic AT 125 |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| CASNo = <!-- blanked - oldvalue: 42228-92-2 --> |
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| UNII = O0X60K76I6 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| PubChem = 294641 |
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| CASNo = 42228-92-2 |
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| CASNo_Ref = {{cascite|changed|CAS}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| PubChem = 294641 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 259938 |
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| ChemSpiderID = 259938 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 74545 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1231101 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C5H7ClN2O3/c6-3-1-2(11-8-3)4(7)5(9)10/h2,4H,1,7H2,(H,9,10)/t2-,4-/m0/s1 |
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| StdInChI = 1S/C5H7ClN2O3/c6-3-1-2(11-8-3)4(7)5(9)10/h2,4H,1,7H2,(H,9,10)/t2-,4-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = QAWIHIJWNYOLBE-OKKQSCSOSA-N |
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| StdInChIKey = QAWIHIJWNYOLBE-OKKQSCSOSA-N |
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| SMILES = Cl\C1=N\O((C(=O)O)N)C1 |
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| SMILES = Cl\C1=N\O((C(=O)O)N)C1 |
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| InChI = InChI=1S/C5H7ClN2O3/c6-3-1-2(11-8-3)4(7)5(9)10/h2,4H,1,7H2,(H,9,10)/t2-,4-/m0/s1 |
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| InChI = InChI=1S/C5H7ClN2O3/c6-3-1-2(11-8-3)4(7)5(9)10/h2,4H,1,7H2,(H,9,10)/t2-,4-/m0/s1 |
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}} |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=5|H=7|Cl=1|N=2|O=3 |
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| C=5 | H=7 | Cl=1 | N=2 | O=3 |
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| MolarMass = 178.574 |
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| MolarMass = 178.574 |
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| Section3 = {{Chembox Hazards |
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'''Acivicin''' is an analog of ]. It is an ] of ]. |
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It is a ] product of '']''.<ref name=Allen>{{ cite journal | last1 = Allen | first1 = L. | last2 = Meck | first2 = R. | last3 = Yunis | first3 = A. | title = The Inhibition of γ-Glutamyl Transpeptidase from Human Pancreatic Carcinoma Cells by (αS,5S)-α-Amino-3-chloro-4,5-dihydro-5-isoxazoleacetic Acid (AT-125; NSC-163501) | journal = Research Communications in Chemical Pathology and Pharmacology| year = 1980 | volume = 27 | issue = 1 | pages = 175–182 |
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| pmid = 6102405 }}</ref> It interferes with glutamate metabolism and inhibits glutamate dependent synthesis of ]s, and is thereby potentially helpful in treatment of ]s.<ref>{{ cite journal | last1 = Hidalgo | first1 = M. | last2 = Rodriguez | first2 = G. | last3 = Kuhn | first3 = J. G. | last4 = Brown | first4 = T. | last5 = Weiss | first5 = G. | last6 = MacGovren | first6 = J. P. | last7 = von Hoff | first7 = D. D. | last8 = Rowinsky | first8 = E. K. | title = A Phase I and Pharmacological Study of the Glutamine Antagonist Acivicin with the Amino Acid Solution Aminosyn in Patients with Advanced Solid Malignancies | journal = Clinical Cancer Research | year = 1998 | volume = 4 | issue = 11 | pages = 2763–2770 | pmid = 9829740 }}</ref> |
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After its discovery in 1972, acivicin was studied as an anti-cancer agent, but trials were unsuccessful due to toxicity.<ref>{{Cite journal|doi = 10.1039/C4SC02339K|title = Target discovery of acivicin in cancer cells elucidates its mechanism of growth inhibition|year = 2015|last1 = Kreuzer|first1 = Johannes|last2 = Bach|first2 = Nina C.|last3 = Forler|first3 = Daniel|last4 = Sieber|first4 = Stephan A.|journal = Chemical Science|volume = 6|issue = 1|pages = 237–245|pmid = 25580214|pmc = 4285139}}</ref> |
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==Research== |
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An in vitro study showed that Acivicin at a concentration of 5 μM Acivicin inhibited by 78% the growth of human ] ] ] (]) after 72 hours in continuous culture. It was also found that acivicin at a concentration of 450 μM irreversibly inactivated MIA PaCa-2 γ-glutamyl transpeptidase (10 nmol/min/10<sup>6</sup> cells) with an inactivation half-life of 80 minutes.<ref name=Allen/> |
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===Phase I studies=== |
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Phase I dose escalating studies conducted in 23 cancer patients administered acivicin with a concomitant 96-h i.v. infusion of a mixture of 16 amino acids showed reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion and decreased mental status. |
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==References== |
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{{Reflist}} |
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==External links== |
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* {{ cite journal | last1 = Obrador | first1 = E. | last2 = Carretero | first2 = J. | last3 = Ortega | first3 = A. | last4 = Medina | first4 = I. | last5 = Rodilla | first5 = V. | last6 = Pellicer | first6 = J. A. | last7 = Estrela | first7 = J. M. | title = γ-Glutamyl Transpeptidase Overexpression Increases Metastatic Growth of B16 Melanoma Cells in the Mouse Liver | journal = Hepatology | year = 2002 | volume = 35 | issue = 1 | pages = 74–81 | doi = 10.1053/jhep.2002.30277 | pmid = 11786961 | doi-access = free }} |
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* {{ cite journal | last1 = Schmees | first1 = C. | last2 = Prinz | first2 = C. | last3 = Treptau | first3 = T. | last4 = Rad | first4 = R. | last5 = Hengst | first5 = L. | last6 = Voland | first6 = P. | last7 = Bauer | first7 = S. | last8 = Brenner | first8 = L. | last9 = Schmid | first9 = R. M. | last10 = Gerhard | first10 = M. | title = Inhibition of T-Cell Proliferation by ''Helicobacter pylori'' γ-Glutamyl Transpeptidase | journal = Gastroenterology | year = 2007 | volume = 132 | issue = 5 | pages = 1820–1833 | doi = 10.1053/j.gastro.2007.02.031 | pmid = 17484877 | doi-access = free }} |
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{{Leukotrienergics}} |
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{{antineoplastic-drug-stub}} |