Acivicin

Acivicin

Names
IUPAC name (2S)-Amino[(5S)-3-chloro-4,5-dihydro-1,2-oxazol-5-yl]ethanoic acid
Other names Antibiotic AT 125
Identifiers
CAS Number	42228-92-2 N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:74545 N
ChEMBL	ChEMBL1231101 N
ChemSpider	259938 Y
PubChem CID	294641
UNII	O0X60K76I6 Y
CompTox Dashboard (EPA)	DTXSID0046010
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 Y Key: QAWIHIJWNYOLBE-OKKQSCSOSA-N Y 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
SMILES Cl\C1=N\O[C@H]([C@@H](C(=O)O)N)C1
Properties
Chemical formula	C5H7ClN2O3
Molar mass	178.574
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Acivicin is an analog of glutamine. It is an inhibitor of gamma-glutamyl transferase.

It is a fermentation product of Streptomyces sviceus. It interferes with glutamate metabolism and inhibits glutamate dependent synthesis of enzymes, and is thereby potentially helpful in treatment of solid tumors.

After its discovery in 1972, acivicin was studied as an anti-cancer agent, but trials were unsuccessful due to toxicity.

Research

An in vitro study showed that Acivicin at a concentration of 5 μM Acivicin inhibited by 78% the growth of human pancreatic carcinoma cells (MIA PaCa-2) 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/10⁶ cells) with an inactivation half-life of 80 minutes.

Phase I studies

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.

External links

• Obrador, E.; Carretero, J.; Ortega, A.; Medina, I.; Rodilla, V.; Pellicer, J. A.; Estrela, J. M. (2002). "γ-Glutamyl Transpeptidase Overexpression Increases Metastatic Growth of B16 Melanoma Cells in the Mouse Liver". Hepatology. 35 (1): 74–81. doi:10.1053/jhep.2002.30277. PMID 11786961.
• Schmees, C.; Prinz, C.; Treptau, T.; Rad, R.; Hengst, L.; Voland, P.; Bauer, S.; Brenner, L.; Schmid, R. M.; Gerhard, M. (2007). "Inhibition of T-Cell Proliferation by Helicobacter pylori γ-Glutamyl Transpeptidase". Gastroenterology. 132 (5): 1820–1833. doi:10.1053/j.gastro.2007.02.031. PMID 17484877.