Aminooxyacetic acid hemihydrochloride

Names

[ Name ]:
Aminooxyacetic acid hemihydrochloride

[Synonym ]:
O-Carboxymethylhydroxylamine hemihydrochloride
(Aminooxy)acetic acid hydrochloride (2:1)
2-aminooxyacetic acid
(carboxymethoxy)amine hemihydrochloride
Acetic acid, 2-(aminooxy)-, hydrochloride (2:1)
Carboxymethoxylamine-D2
Aminyloxy-acetic Acid Hemihydrochlorid
2-AMINOOXY-ACETICACIHYDROCHLORIDE
aminooxyaceticacidhemichloride
AMinooxyacetic acid Hydrochloride
O-(carboxymethyl) hydroxylamine hemichloride
2-aminooxy-aceticacihydrochloride(2:1)
Bis((aminooxy)acetic) acid hydrochloride
MFCD00012955
Aminooxyacetic acid hemihydrochloride
2-(Aminooxy)acetic acid hydrochloride(2:1)
(Aminooxy)acetic Acid Hemihydrochloride
(aminooxy)-aceticacihydrochloride(2:1)
CarboxyMethoxylaMine HeMihydrochloride
O-(Carboxymethyl)hydroxylamine hemihydrochloride
Carboxymethoxyamine hemihydrochloride
EINECS 220-862-3
(carbomethoxy)amine hemihydrochloride

Biological Activity

[Description]:

Aminooxyacetic acid hemihydrochloride is a malate-aspartate shuttle (MAS) inhibitor which also inhibits the GABA degradating enzyme GABA-T.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

Research Areas >> Cancer

[Target]

MAS[1], GABA-T[2]

[In Vitro]

Aminooxyacetic acid hemihydrochloride (AOAA) dose-dependently decreases the survival of C6 glioma cells. Aminooxyacetic acid hemihydrochloride treatment produces a significant increase in the percentage of the cells arrested in the stage of G0/G1, as well as a significant decrease in the percentage of the cells at S phase and G2/M phase. Aminooxyacetic acid hemihydrochloride treatment leads to an obvious decrease in the number of the cells in the phase of cell division. Aminooxyacetic acid hemihydrochloride significantly increases the percentage of the cells in both early-stage apoptosis and necrosis. Treatment of the cells with 1 mM or 5 mM Aminooxyacetic acid hemihydrochloride leads to decreased levels of aging of the cells[1]. Glutamine-dependent cell lines show greater inhibition of cell growth by Aminooxyacetic acid hemihydrochloride (AOA) compare with cells that are less glutamine dependent[3].

[In Vivo]

The accumulation of GABA in cerebellum and whole brain is initially very rapid, being significantly increased already 5 min after the injection of Aminooxyacetic acid hemihydrochloride (AOAA). The rapid initial accumulation becomes gradually slower and maximal levels (400 to 600 % of the control levels) are reached 2 to 6 h after Aminooxyacetic acid hemihydrochloride. Still 24 h after Aminooxyacetic acid hemihydrochloride the GABA levels are elevated by about 250%. From 2 to 6 h after Aminooxyacetic acid hemihydrochloride the convulsions are completely blocked. Twenty four hours after Aminooxyacetic acid hemihydrochloride the convulsions are almost identical to the controls[2].

[Kinase Assay]

Enzyme activity of aspartate transaminase is measured by a colorimetric assay assessing formation of pyruvate from oxaloacetate, a product of GOT1/2 (also called AST1/2) activity, as described previously. In brief, cells grown in 6-well plates are collected after 6, 24, or 48 hours of Aminooxyacetic acid hemihydrochloride (AOA) treatment and washed with cold PBS, lysed, and supernatant used for analysis[3].

[Cell Assay]

Breast cancer cell lines are used in this study. Cells are plated in 96-well plates at 1,500 to 5,000 cells per well in 100 μL media. New medium with varying concentration of Aminooxyacetic acid hemihydrochloride (AOA) is added after 12 hours. The assay is performed after 48 hours[3].

[Animal admin]

Female albino rats (150 to 200 g) bred at our department are used. Aminooxyacetic acid hemihydrochloride (AOAA) is injected into a tail vein (2 mL/kg body weight). For this purpose the rat is placed in a plastic tube and the tail warmed in water 42°C[2].

[References]

[1]. Wang C, et al. Malate-aspartate shuttle inhibitor aminooxyacetic acid leads to decreased intracellular ATP levels and altered cell cycle of C6 glioma cells by inhibiting glycolysis. Cancer Lett. 2016 Aug 1;378(1):1-7.

[2]. Pagliusi SR, et al. Aminooxyacetic acid induced accumulation of GABA in the rat brain. Interaction with GABA receptors and distribution in compartments. Naunyn Schmiedebergs Arch Pharmacol. 1983 Apr;322(3):210-5.

[3]. Korangath P, et al. Targeting Glutamine Metabolism in Breast Cancer with Aminooxyacetate. Clin Cancer Res. 2015 Jul 15;21(14):3263-73.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
326.7ºC at 760 mmHg

[ Melting Point ]:
156 °C (dec.)(lit.)

[ Molecular Formula ]:
NH₂OCH₂COOH·_0.5HCl

[ Molecular Weight ]:
109.30

[ Flash Point ]:
151.4ºC

[ PSA ]:
145.10000

[ LogP ]:
0.12520

[ Vapour Pressure ]:
4.24E-05mmHg at 25°C

[ Storage condition ]:
-20°C Freezer

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AF3150000

CAS REGISTRY NUMBER :: 2921-14-4

LAST UPDATED :: 199701

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C4-H10-N2-O6.Cl-H

MOLECULAR WEIGHT :: 218.62

WISWESSER LINE NOTATION :: ZO1VQ 2 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 65 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JMPCAS Journal of Medicinal and Pharmaceutical Chemistry. (Washington, DC) V.1-5, 1959-62. For publisher information, see JMCMAR. Volume(issue)/page/year: 5,464,1962

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 91 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Skin and Appendages - hair

REFERENCE :: NEPHBW Neuropharmacology. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.9- 1970- Volume(issue)/page/year: 21,803,1982

Safety Information

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
UN 1193 3/PG 2

[ WGK Germany ]:
3

[ RTECS ]:
AF3150000

[ Packaging Group ]:
II

[ Hazard Class ]:
3

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Synthesis and in vitro antibacterial properties of 2-(3-bromo-5-isoxazolylideneamino-oxy)acetamido-beta-lactam derivatives.

Il Farmaco 46 , 887, (1991)

The synthesis of new 2-(3-bromo-5-isoxazolylideneamino-oxy)acetic acids and their condensation derivatives with suitable beta-lactam nuclei is reported. Their antibacterial properties have been tested...

Tetrahedron Lett. 34 , 4347, (1993)