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89464-63-1

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89464-63-1 Usage

Description

The pro-angiogenic factor HIF-1α is targeted for destruction in normoxic environments by the hydroxylation of a specific proline residue, P564, by the oxygen-sensing enzyme HIF-1α prolyl hydroxylase (HIF-PH). DMOG is a cell permeable, competitive inhibitor of HIF-PH. It acts to stabilize HIF-1α expression at normal oxygen tensions in cultured cells, at concentrations between 0.1 and 1 mM. DMOG is therefore expected to act as a pro-angiogenic compound, acting via the HIF-1α system.

Chemical Properties

Off-White to Pale Pink Solid

Uses

Different sources of media describe the Uses of 89464-63-1 differently. You can refer to the following data:
1. DMOG is a cell permeable prolyl-4-hydroxylase inhibitor which upregulates HIF activity. HIF activation stimulates angiogenesis in several different models (1nM). DMOG also inhibits FIH (factor inhibiting HIF), an asparaginyl hydroxylase, which enhances the HIF response. It is active in vivo and attenuates myocardial injury in a rabbit ischemia reperfusion model (20mg/Kg).
2. DMOG is a cell permeable prolyl-4-hydroxylase inhibitor that regulates hypoxia-inducible factor

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

Check Digit Verification of cas no

The CAS Registry Mumber 89464-63-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,9,4,6 and 4 respectively; the second part has 2 digits, 6 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 89464-63:
(7*8)+(6*9)+(5*4)+(4*6)+(3*4)+(2*6)+(1*3)=181
181 % 10 = 1
So 89464-63-1 is a valid CAS Registry Number.
InChI:InChI=1/C6H9NO5/c1-11-4(8)3-7-5(9)6(10)12-2/h3H2,1-2H3,(H,7,9)

89464-63-1 Well-known Company Product Price

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  • Sigma

  • (D3695)  DMOG  ≥98% (HPLC)

  • 89464-63-1

  • D3695-10MG

  • 872.82CNY

  • Detail
  • Sigma

  • (D3695)  DMOG  ≥98% (HPLC)

  • 89464-63-1

  • D3695-50MG

  • 3,517.02CNY

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89464-63-1SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 19, 2017

Revision Date: Aug 19, 2017

1.Identification

1.1 GHS Product identifier

Product name Dimethyloxalylglycine

1.2 Other means of identification

Product number -
Other names methyl 2-[(2-methoxy-2-oxoethyl)amino]-2-oxoacetate

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
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More Details:89464-63-1 SDS

89464-63-1Relevant articles and documents

Triflic anhydride-mediated synthesis of oxazoles

Thalhammer, Armin,Mecinovi?, Jasmin,Schofield, Christopher J.

supporting information; experimental part, p. 1045 - 1047 (2009/05/31)

N-Acyl amino acid esters undergo triflic anhydride-mediated cyclodehydration to form oxazoles and bisoxazoles in a simple one-pot transformation.

Selective inhibition of factor inhibiting hypoxia-inducible factor

McDonough, Michael A.,McNeill, Luke A.,Tilliet, Melanie,Papamicael, Cyril A.,Chen, Qiu-Yun,Banerji, Biswadip,Hewitson, Kirsty S.,Schofield, Christopher J.

, p. 7680 - 7681 (2007/10/03)

A set of four non-heme iron(II) and 2-oxoglutarate-dependent enzymes catalyze the post-translational modification of a transcription factor, hypoxia inducible factor (HIF), that mediates the hypoxic response in animals. Hydroxylation of HIF both causes it

A novel [2 + 3] cycloaddition reaction: Singlet oxygen mediated formation of 1,3-dipole from iminodiacetic acid dimethyl ester and its addition to maleimides

Cheng,Gan,Shi,Wei

, p. 6369 - 6374 (2007/10/03)

Sensitized photolysis of iminodiacetic acid methyl ester and maleimides follows a [2 + 3] cycloaddition pathway yielding pyrrolidine derivatives. This is similar to the photochemical reaction between C60 and amines. A series of pyrrolidine derivatives are prepared by the method including multipyrrolidines from bis- and tris-maleimide starting materials. The yields range from 13% to 85%. The reaction is highly stereoselective. All the isolated products have the 1,3-dimethoxycarbonyl groups in the cis configuration. Various sensitizers may be used with slightly different yields. A plausible mechanism is proposed that involves the singlet oxygen abstraction of two α hydrogen atoms from the iminodiacetate and formation of a 1,3-dipole with a structure similar to the classical thermally generated 1,3-dipole.

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