89464-63-1

Basic information

• Product Name: DMOG
• Synonyms: N-(METHOXYOXOACETYL)-GLYCINE METHYL ESTER;DIMETHYLOXALLYL GLYCINE;DIMETHYLOXALYLGLYCINE;DMOG;Dimethyloxaloylglycine;N-[(Methoxycarbonyl)Methyl]oxaMic Acid Methyl Ester;DiMethyloxaloylglycine (DMOG);N-(2-Methoxy-2-oxoacetyl)glycine methyl ester
• CAS NO: 89464-63-1
• Molecular Formula: C₆H₉NO₅
• Molecular Weight: 175.14
• EINECS: 200-256-5
• Product Categories: Bio-material;NONE;Amino Acids 13C, 2H, 15N;Amino Acids & Derivatives;Inhibitors;Other
• Mol File: 89464-63-1.mol

Chemical Properties

• Melting Point: 46-48°C
• Boiling Point: 179-182 °C(Press: 12 Torr)
• Appearance: white to off-white/Solid
• Density: 1.247g/cm3
• Refractive Index: 1.44
• Storage Temp.: Refrigerator
• Solubility: H2O: >30mg/mL
• PKA: 10.55±0.46(Predicted)
• Water Solubility: Soluble in water at 30mg/ml.
• Stability: Stable for 2 years from date of purchase as supplied. Solutions are not stable. Solutions must be made fresh and used within 1 working day.
• CAS DataBase Reference: DMOG(CAS DataBase Reference)
• NIST Chemistry Reference: DMOG(89464-63-1)
• EPA Substance Registry System: DMOG(89464-63-1)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 89464-63-1(Hazardous Substances Data)

Usage

Uses

Used in Angiogenesis Research:
DMOG is used as a pro-angiogenic compound for stimulating angiogenesis in various models due to its ability to activate HIF, which in turn promotes the formation of new blood vessels.
Used in Hypoxia Signaling Pathway Studies:
In the field of cellular and molecular biology, DMOG is utilized as a research tool to investigate the hypoxia signaling pathway by inhibiting HIF-PH and stabilizing HIF-1α.
Used in Cardiovascular Research:
DMOG is used as a therapeutic agent for attenuating myocardial injury in ischemia reperfusion models, demonstrating its potential in treating cardiovascular conditions.
Used in Drug Development:
In the pharmaceutical industry, DMOG serves as a lead compound for the development of new drugs targeting the HIF pathway, which has implications for treating various diseases, including anemia, cancer, and ischemic disorders.

Biochem/physiol Actions

DMOG is a cell permeable prolyl-4-hydroxylase inhibitor, which upregulates HIF (hypoxia-inducible factor). The protein level of HIF-1α subunit is post-transcriptionally regulated by prolyl and asparaginyl hydroxylase (PAH). Suppression of PAH activity increases endogenous HIF-1α levels. DMOG is a cell permeable, competitive inhibitor of prolyl hydroxylase domain-containing proteins (PHDs and HIF-PHs). It has been discovered that the DMOG posseses neuroprotective effect on NFG deprived cell cultures through preservation of glucose metabolism. DMOG also attenuates myocardial injury in a rabbit ischemia reperfusion model. DMOG is more potent than the older inhibitor 4-Phenyl-pyridine-2,5-dicarboxylic acid (R395889; Sigma-Aldrich rare chemicals library). The IC50 is 5.18 μM.

in vitro

dmog acts to stabilize hif-1a expression under normal oxygen tension in cultured cells at concentrations from 0.1 to 1 mmol/l [2].

Enzyme inhibitor

This iron-binding a-ketoglutarate (2-oxoglutarate) analogue (FW = 147.09 g/mol; also named N-oxaloglycine) competitively inhibits prolyl-4- hydroxylase (Reaction: Procollagen (L-proline) + a-ketoglutarate + O2 → Procollagen ( (2S,4R) -4-hydroxyproline) + succinate + CO2). During catalysis, prolyl-4-hydroxylase forms Fe (III), and the latter most likely makes an extremely stable metal ion complex with N-oxaloglycine. Substitution on the glycine moiety alters inhibitor activity stereoselectively and that, if the w-carboxylate is homologated or replaced, either by acylsulfonamides or anilide, activity is likewise sharply reduced. Prolyl- 4-Hydroxylase Catalysis: Each catalytic round of this posttranslational modifying enzyme reaction occurs in two stages. O2 is bound end-on in an axial position, producing a dioxygen unit. Nucleophilic attack at C-2 generates a tetrahedral intermediate, with loss of the double bond in dioxygen and bonds to iron and the a-carbon of a-ketoglutarate. Elimination of CO2 coincides with formation of the Fe (IV) =O species. The second stage involves the abstraction of the pro-R hydrogen atom from C-4 of proline, followed by radical combination, yielding hydroxyproline. In the presence of a-ketoglutarate, enzyme-bound Fe2+ is rapidly converted to Fe3+, resulting in inactivation of the enzyme Ascorbate is utilized as a cofactor to reduce Fe (III) back to Fe (II). Cell-Permeable Analogue: Dimethyloxalylglycine (FW = 175.14 g/mol; CAS 89464-63-1; Symbol: DMOG, also named N- (methoxyoxoacetyl) -glycine methyl ester) is metabolicaly demethylated to form N-oxaloglycine upon entry to many cells.

in vivo

pre-treatment with dmog attenuates systemic lps-induced activation of the nf-κb pathway. furthermore, mice treated with dmog had significantly increased survival in lps-induced shock. in addition, in vivo dmog treatment upregulates the expression of il-10, specifically in the peritoneal b-1 cell population [3].

IC 50

9.3 and 3.7 μm for hydroxyproline synthesis inhibition of embryonic chicken lung extracted from tissue and culture medium [1].

References

1) Asikainen et al. (2005), Activation of hypoxia-inducible factors in hyperoxia through prolyl 4-hydroxylase blockade in cells and explants of primate lung; Proc. Natl. Acad. Sci. USA, 102 10212 2) Jaakkola et al. (2001), Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation; Science, 292 468 3) Hamada et al. (2009), Synthesis and activity of N-oxalylglycine and it’s derivatives as jumonji C-domain-containing histone lysine demethylase inhibitors; Bioorg. Med. Chem. Lett., 19 2852 4) Lomb et al. (2009), Prolyl hydroxylase inhibitors depend on extracellular glucose and hypoxia-inducible factor (HIF)-2alpha to inhibit cell death caused by nerve growth factor deprivation: evidence that HIF-2alpha has a role in NGF-promoted survival of sympathetic neurons; Mol. Pharmacol., 75 1198 5) Xie et al. (2012), PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response; J. Clin. Invest., 122 2827

InChI:InChI=1/C6H9NO5/c1-11-4(8)3-7-5(9)6(10)12-2/h3H2,1-2H3,(H,7,9)

Upstream product

• 5781-53-3 monomethyl oxalyl chloride 
• 5680-79-5 glycine ethyl ester hydrochloride 
• 6096-81-7 dimethyl iminodiacetate 
• 553-90-2 Dimethyl oxalate 

Downstream Products

• 477870-14-7 methyl 5-methoxy-1,3-oxazole-2-carboxylate 

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