Dimethyloxalylglycine

Names

[ Name ]:
Dimethyloxalylglycine

[Synonym ]:
Glycine, N-(2-methoxy-1,2-dioxoethyl)-, methyl ester
Dimethyloxalylglycine
methyl 2-[(2-methoxy-2-oxoethyl)amino]-2-oxoacetate
Methyl N-[methoxy(oxo)acetyl]glycinate
DMOG

Biological Activity

[Description]:

DMOG (Dimethyloxallyl Glycine) is a cell-permeable and competitive inhibitor of HIF-1α prolyl hydroxylase (HIF-PH).

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> HIF/HIF Prolyl-Hydroxylase

Research Areas >> Cancer

[Target]

HIF-1α prolyl hydroxylase[1]

[In Vitro]

DMOG efficiently suppresses hydroxyproline synthesis in intact cells, but shows only weakly active in the microsomal system[1]. DMOG reduces FGF-2-induced proliferation and cyclin A expression by inhibiting prolyl hydroxylase activity in HPASMC[3].

[In Vivo]

DMOG inhibits endogenous HIF inactivation, and induces angiogenesis in ischaemic skeletal muscles of mice[2]. Up-regulation of hypoxia-inducible factor-1α by DMOG enhances the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats[4].

[Cell Assay]

To analyze DNA synthesis as an index of cellular proliferation, VSMC are plated in 48-well plates (5,000 per square centimeter) in growth medium, incubated overnight, and serum-deprived (1% FCS) for 24 h. Replicate wells are then stored at −70°C for baseline (day 0) cell counts, and fresh medium with or without growth factors is added to the remaining wells, which are incubated 72-96 h in 20 or 5% O2. Days 0 and 3 or 4 cell counts are determined by lysing cells in a buffer containing a fluorescent dye, which has minimal fluorescence by itself but fluoresces when bound to DNA or RNA. Absolute cell numbers are calculated by comparing the fluorescence of specimens with that of a standard curve similarly prepared using a known number of cells.

[Animal admin]

Two groups of mice (C57Bl6) are subjected to unilateral femoral artery ligation under fluothane inhalation anaesthesia (2% in O2). One group (n=11) receives dimethyloxalylglycine (DMOG) i.p. (8 mg in 0.5 mL saline) on days 1, 3, 5, 7 and 9 while the animals in the other group are injected with sterile saline (0.5 mL) at the same intervals (n=6). A third group is treated with DMOG without ligation (n=4) and four unoperated mice serve as controls. After 11 days mice are terminally anaesthetized and the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles excised.

[References]

[1]. Baader E, et al. Inhibition of prolyl 4-hydroxylase by oxalyl amino acid derivatives in vitro, in isolated microsomes and in embryonic chicken tissues. Biochem J. 1994 Jun 1;300 (Pt 2):525-30.

[2]. Milkiewicz M, et al. Inhibition of endogenous HIF inactivation induces angiogenesis in ischaemic skeletal muscles of mice. J Physiol. 2004 Oct 1;560(Pt 1):21-6.

[3]. Schultz K, et al. Prolyl hydroxylase 2 deficiency limits proliferation of vascular smooth muscle cells by hypoxia-inducible factor-1{alpha}-dependent mechanisms. Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L921-7.

[4]. Li X, et al. Up-regulation of hypoxia-inducible factor-1α enhanced the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats. Acta Biochim Biophys Sin (Shanghai). 2014 Feb;46(2):112-8.

[Related Small Molecules]

PT-2385 | FG-4592 | PX-478 2HCl | BAY 87-2243 | Vadadustat | Daprodustat | Oltipraz | Chlorogenic acid | LW 6 | Molidustat | IOX2 | Paeoniflorin | KC7F2 | oroxylin A | JNJ-42041935

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Melting Point ]:
46-48ºC

[ Molecular Formula ]:
C₆H₉NO₅

[ Molecular Weight ]:
175.139

[ Exact Mass ]:
175.048065

[ PSA ]:
81.70000

[ LogP ]:
-0.56

[ Appearance of Characters ]:
Solid | white to off-white

[ Index of Refraction ]:
1.440

[ Storage condition ]:
Refrigerator

[ Water Solubility ]:
H2O: >30mg/mL | Soluble in water at 30mg/ml.

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R22

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2924199090

Synthetic Route

Click to get detail synthetic route

Customs

[ HS Code ]: 2924199090

[ Summary ]:
2924199090. other acyclic amides (including acyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles

Anti-chondroitin sulfate proteoglycan 4-specific antibodies modify the effects of vemurafenib on melanoma cells differentially in normoxia and hypoxia.

Int. J. Oncol. 47 , 81-90, (2015)

Chondroitin sulfate proteoglycan 4 (CSPG4), a highly immunogenic melanoma tumor antigen, is a potential target for antibody-based immunotherapy. The mechanism by which CSPG4 affects melanoma progressi...

A novel effect of DMOG on cell metabolism: direct inhibition of mitochondrial function precedes HIF target gene expression.

Biochim. Biophys. Acta 1847 , 1254-66, (2015)

Abnormal accumulation of oncometabolite fumarate and succinate is associated with inhibition of mitochondrial function and carcinogenesis. By competing with α-ketoglutarate, oncometabolites also activ...

Hypoxia lowers SLC30A8/ZnT8 expression and free cytosolic Zn2+ in pancreatic beta cells.

Diabetologia 57(8) , 1635-44, (2014)

Hypoxic damage complicates islet isolation for transplantation and may contribute to beta cell failure in type 2 diabetes. Polymorphisms in the SLC30A8 gene, encoding the secretory granule zinc transp...

Related Compounds

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