Mouse microsomes activate MeIQx (0.47 mM; 0-120 min) to produce metabolites through covalent binding to mouse hemoglobin [1].

MeIQx (2.0-200 mg/kg; i.p.; male Swiss Webster mice) covalently binds to hemoglobin in a dose-dependent manner [1].

Animal/Disease Models: Male Swiss Webster mouse [1]
Doses: 2.0-200 mg/kg
Route of Administration: intraperitoneal (ip) injection
Experimental Results: Increased covalent binding to hemoglobin in a dose-dependent manner.

Absorption, Distribution and Excretion
Cooking meat, fish, or poultry at high temperature gives rise to heterocyclic aromatic amines (HAAs), which may be metabolically activated to mutagenic or carcinogenic intermediates. The enzymes cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) are principally implicated in such biotransformations ... The relationship between the activity of these two enzymes and the urinary excretion of unmetabolized and Phase II conjugates of the two HAAs MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) /was determined/ in individuals fed a uniform diet containing high-temperature cooked meat. The subjects in the study ate meat containing known amounts of MeIQx and PhIP, and urine collections were made 0-12 and 12-24 hr after a meal. MeIQx and PhIP were measured in urine after acid treatment that quantitatively hydrolyzes the Phase II conjugates to the respective parent amine. The extracts containing the HAAs were purified by immunoaffinity chromatography and analyzed by liquid chromatography using electrospray ionization-tandem mass spectrometry. The MeIQx content in the 0-12 hr urine increased after acid hydrolysis by a factor of 3-21-fold. After acid treatment, the total amount of MeIQx (unmetabolized plus the N2-glucuronide and sulfamate metabolites) excreted in the 0-12 hr urine was 10.5 +/- 3.5% (mean +/- SD) of the dose, whereas the total amount of PhIP (unmetabolized plus acid-labile conjugate(s)) in the 0-12 hr period was 4.3 +/- 1.7% (mean +/- SD) of the dose. The total amount of PhIP in the 12-24 hr urine after acid treatment was 0.9 +/- 0.4% (mean +/- SD) of the dose. Linear regression analysis of the amounts of MeIQx and PhIP excreted in the 0-12 hr period expressed as a percentage of the ingested dose, for all subjects, gave a low but significant correlation (r = 0.37, P = 0.005). Linear regression analyses showed that lower total MeIQx (unmetabolized plus the N2-glucuronide and sulfamate metabolites) in urine was associated with higher CYP1A2 activity, whereas total PhIP (unmetabolized plus conjugated) in urine showed no association to CYP1A2 activity. These results indicate that in humans, MeIQx metabolism and disposition are more strongly influenced by CYP1A2 activity than are those of PhIP. Linear regression analysis found no association between NAT2 activity and the levels (unmetabolized plus acid-labile conjugates) of MeIQx or PhIP excreted in urine.
The kinetics of distribution of radiolabelled [2-14]C-IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and [2-14]C-MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) following the oral administration to BALB/c mice of single doses were studied. Both compounds were taken up into the blood-stream and other tissues rapidly after administration, and approx 20-25% of the radioactive dose of IQ or MeIQx was excreted in urine over 6 hr, reflecting the rapid absorption of the mutagens. Significantly greater levels of MeIQx than IQ were isolated from the lungs and blood of treated mice. In studies of the uptake of IQ from closed sections of the gut, little IQ was absorbed from the stomach. Although there was some evidence that it could be absorbed from the large intestine, the primary site of IQ absorption was the small intestine.
The absorption and kinetics of excretion of (14)C-2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) was studied in male Sprague-Dawley rats. Within 72 hr of an oral dose of (14)C-MeIQx (20 mg/kg) 33-56% of the radioactivity was excreted in the urine and 37-75% of the radioactivity in the feces, which accounted for greater than 99% of the dose. Only low levels of radioactivity remained in the body. Radioactivity, when expressed per gram of tissue, was highest in the liver and kidney with smaller amounts detected in the lung and both the small and large intestines. Between 25 and 50% of a dose of MeIQx was recovered in the bile within 24 hr. Biliary metabolites were excreted over a long period of time with one radioactive fraction rapidly excreted at 2-3 hr and a second fraction excreted at 10-12 hr. The metabolites present in bile were assessed for genotoxicity using Salmonella typhimurium TA98 with or without hepatic S-9 activation and were found to be present as detoxified products. The residual mutagenic activity present in bile was attributed primarily to unmetabolized MeIQx.
The disposition and metabolism of ... 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was studied in rats. Five rats of both sexes were given a single oral dose of (14)C-labeled MeIQx (3-4 mg/kg bw). The male rats excreted 36% of the radioactivity and 15% of the mutagenic activity of the dose given in the urine collected during the first 24 hr. In the females the corresponding urine contained 41% of the radioactivity and 12% of the mutagenicity. During the next 48 hr only 1-3% of the radioactive dose was excreted in urine. The remaining dose was excreted in the feces except for less than 1% that was retained by the tissues after 72 hr. The liver and kidney retained more radioactivity than other organs.
For more Absorption, Distribution and Excretion (Complete) data for 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
2-Amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) ... and its isotopically labelled ([13]C, [15]N2 and [14]C) analogues were synthesized and used for metabolic studies in vivo. An equimolar mixture of MeIQx and its [13]C, [15]N2 stable isotope labelled analogue (containing tracer amounts of [14]C-MeIQx) was given ip to mice. Some 67% of the radioactivity was eliminated in urine and feces within 24 hr. Four radiolabelled species were observed when urine was analysed by HPLC, corresponding to unchanged MeIQx and three more polar metabolites. Urine was analysed directly by HPLC-thermospray mass spectrometry. Four signals were observed containing the characteristic 1:1 isotopic doublet, corresponding to unchanged MeIQx, an MeIQx glucuronide, and two uncharacterized metabolites.
Adduct formation has been considered to be a major causal factor of DNA damage by carcinogenic heterocyclic amines. By means of experiments with (32)P-labeled DNA fragments and an electrochemical detector coupled to a high-pressure liquid chromatograph, we investigated whether the N-hydroxy metabolite of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) can cause oxidative DNA damage or not. This metabolite [MeIQx(NHOH)] was found to cause Cu(II)-mediated DNA damage, including 8-oxo-7,8-dihydro-2'-deoxyguanosine formation. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH), was added, the DNA damage was greatly enhanced. Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). MeIQx(NHOH) frequently induced DNA cleavage at thymine and cytosine residues in the presence of NADH and Cu(II). A UV-visible spectroscopic study showed that little decomposition of MeIQx(NHOH) occurred in the absence of Cu(II), whilst rapid spectral change was observed in the presence of Cu(II), suggesting that Cu(II) catalyzes the autoxidation. The addition of NADH reduced the oxidized product back to MeIQx(NHOH). These results suggest that a copper-peroxo intermediate, derived from the reaction of Cu(I) with H2O2, participates in Cu(II)-dependent DNA damage by MeIQx(NHOH), and NADH enhances the DNA damage via a redox cycle. /It was concluded/ that in addition to DNA adduct formation, oxidative DNA damage plays an important role in the carcinogenic process of MeIQx. /MeIQx (NHOH)/
2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), one of the most abundant of the heterocyclic aromatic amines formed during the cooking of meat, is genotoxic and carcinogenic in rodents. MeIQx requires metabolic activation by P450 before it can exert these effects. While there is indirect evidence that the mutagenic product is N-hydroxy-MeIQx (N-OHMeIQx), ... this /was identified/ unequivocally following incubation of the amine with human hepatic microsomal fraction. A mixture of unlabelled MeIQx, (13C,15N2)MeIQx and (14C)MeIQx was used as substrate and the products analysed by HPLC-thermospray mass spectrometry. Characteristic doublet ions, 3 mass units apart, were found at m/z 214/217 ([M+H]+) from the parent compound, MeIQx and at 230/233 ([M+H]+) from N-OHMeIQx. The presence of a doublet ion at m/z 214/217 with the doublet at 230/233 [M+H+] provided additional evidence that this was N-OHMeIQx, as facile loss of 'O' is characteristic of N-hydroxylamines. Further evidence for the identity of the major metabolite, which accounted for approximately 90% of all microsomal metabolism, was obtained by comparing the mutagenicity of the HPLC eluate using Salmonella typhimurium YG1024, which is particularly sensitive to N-hydroxylamines, and TA98/1,8-DNP6 which is resistant to most N-hydroxylamines. Ninety-five per cent of direct-acting mutagenicity present in the reaction mixture was associated with a single peak, which co-eluted with N-OHMeIQx, as indicated by mass spectrometry. In the presence of a metabolic activation system, only one additional mutagenic peak, corresponding to unchanged MeIQx, could be detected. MeIQx (5 microM) was N-hydroxylated at a rate of 77 +/- 11 pmol/mg/min (mean +/- SEM, n = 4) by human liver microsomes. The specific inhibitor of human CYP1A2, furafylline (5 uM) inhibited the N-hydroxylation of MeIQx by > 90%. These data show that N-OHMeIQx is both the major oxidation product and the major genotoxic product of MeIQx generated by microsomal fractions of human liver and that the reaction is catalysed almost exclusively by CYP1A2.
The disposition and metabolism of ... 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was studied in rats. After a single oral dose of 20 mg (14)C-labeled MeIQx/kg bw, three major non-mutagenic metabolites were identified. These were 2-amino-4(or 5)-(beta-D-glucuronopyranosyloxy)-3,8-dimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxalin-4(or 5)-yl sulfate and N-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl) sulfamate. Another two metabolites present in bile, urine and feces were 2-(beta-D-glucuronopyranosylamino)-3,8-dimethylimidazo[4,5-f ] quinoxaline and 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxalin-4 (or 5)yl sulfate. All metabolites were essentially non-mutagenic. Most of the mutagenicity still present in bile, urine and feces could be explained by unchanged MeIQx. Unchanged MeIQx was the most abundant form excreted in urine.
For more Metabolism/Metabolites (Complete) data for 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (20 total), please visit the HSDB record page.
Meiqx has known human metabolites that include IQx-8-COOH and N-HydroxyMeIQX.

[1]. The measurement of MeIQx adducts with mouse haemoglobin in vitro and in vivo: implications for human dosimetry. Carcinogenesis. 1991 Jun;12(6):1067-72.

[2]. Carcinogenicity in mice of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) from cooked foods. 1987 May;8(5):665-8.

MeIQx (2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline) can cause cancer according to The World Health Organization's International Agency for Research on Cancer (IARC).
MeIQx is an imidazoquinoxaline that is 3H-imidazo[4,5-f]quinoxaline substituted at positions 3 and 8 by methyl groups and at position 2 by an amino group. A mutagenic compound found in cooked beef. It has a role as a mutagen, a carcinogenic agent, a genotoxin and a Maillard reaction product. It is an imidazoquinoxaline and an aromatic amine.
8-Methyl-IQX is a synthetic, pale orange to brown crystalline solid that is soluble in dimethylsulfoxide and methanol. It is produced in small quantities for research purposes. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline is formed naturally during the cooking of muscle-derived foods (meat and fish). Levels of this chemical produced in this manner are dependent on cooking temperature, cooking time and method of cooking (direct or indirect). It is one of the most abundant heterocyclic amines in a typical Western diet. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline has also been detected in processed food flavorings, beer, wine, and cigarette smoke. It is reasonably anticipated to be a human carcinogen. (NCI05)
See also: Beef (part of); Chum salmon, cooked (has part); Chicken, cooked (part of) ... View More ...

C11H11N5

213.244

213.101

C, 61.96; H, 5.20; N, 32.84

77500-04-0

MeIQx-d3;122457-31-2

62275

Light yellow to yellow solid powder

1.47 g/cm3

458.4ºC at 760mmHg

> 300ºC

1.776

1.988

1

4

0

16

271

0

CC1=CN=C2C=CC3=C(C2=N1)N=C(N3C)N

DVCCCQNKIYNAKB-UHFFFAOYSA-N

InChI=1S/C11H11N5/c1-6-5-13-7-3-4-8-10(9(7)14-6)15-11(12)16(8)2/h3-5H,1-2H3,(H2,12,15)

3,8-Dimethyl-3H-imidazo(4,5-f)quinoxalin-2-amine

8-Methyl-IQX; MeIQx;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)