Absorption, Distribution and Excretion
This study investigated the metabolism of intravenously injected (14) C-IQ in male NMRI mice, pregnant NMRI mice, and female C3H mice. Whole-body autoradiography revealed the accumulation of the radiolabeled substance in metabolic and excretory organs (liver, kidneys, bile, urine, gastrointestinal contents, salivary glands, nasal mucosa, and Haver glands), lymphoid and myeloid tissues (bone marrow, thymus, spleen, and lymph nodes), and endocrine and reproductive tissues (adrenal medulla, pancreas, thyroid gland, pituitary gland, testes, epididymis, seminal vesicles, ampulla, and prostate). The liver and renal cortex were identified as sites of retention for which the radiolabeled substance could not be extracted. IQ could cross the placenta, but no retention of the radiolabeled substance was detected in fetal tissues.

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Metabolism / Metabolites
This study investigated the metabolism of IQ in male rats by labeling the 2- and 5-positions of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) with C₂₄ and H₃, respectively. Adult male Fischer 344 rats were administered [2-14C]IQ or [5-3H]IQ by gavage at doses of 20 or 40 mg/kg body weight. Additionally, some rats had [2-14C]IQ added to their diet at a concentration of 300 ppm for 2 days; subsequently, unlabeled IQ (300 ppm) was added to their diet for approximately 6.5 weeks, followed by a final 2-day addition. Within the first 48 hours following gavage administration of 20 or 40 mg/kg body weight of [2-14C]IQ, approximately 40-50% of the radioactive material was recovered in the urine and approximately 30-38% in the feces. Within the first 72 hours following ingestion of [2-14C]IQ (300 ppm), approximately 26% of the radioactive material was recovered in the urine and approximately 61% in the feces. Following bile duct cannulation, rats were administered a single dose of [2-14C]IQ (40 mg/kg body weight) orally by gavage; within 2 days, approximately 15% of the administered dose was excreted in the bile. The urine of rats administered [2-14C]IQ contained three major polar metabolites, including glucuronide, sulfate, and IQ sulfamate, as well as several nonpolar metabolites, including IQ, 2-acetamido-3-methylimidazo[4,5-f]quinoline, 2-aminoimidazo[4,5-f]quinoline, and 2-amino-3,6-dihydro-3-methyl-7H-imidazo[4,5-f]quinoline-7-one (7-OH-IQ). The same metabolites were produced by gavage or dietary supplementation with [2-14C]IQ, but in different amounts. In the feces of rats administered [2-14C]IQ by gavage, the major polar metabolite was IQ sulfamate. Similar nonpolar metabolites were also present in the feces as in the urine, but in different amounts. The predominant nonpolar fecal metabolite 7-OH-IQ is likely a result of gut microbiota activity. Compared to animals fed [2-14C]IQ, rats given a single oral gavage of [2-14C]IQ showed higher urinary excretion of metabolites and lower fecal excretion. One polar metabolite present in urine, IQ-sulfamate (39%), was present at significantly higher levels in rats given oral IQ than in those fed IQ (less than 6%). Therefore, IQ is extensively metabolized, producing a variety of polar and nonpolar metabolites, the amounts of which depend in part on the route of administration. Both mixed and pure cultures of human gut anaerobic bacteria metabolize IQ to IQ-7-one. Dietary components may play a role in IQ metabolism. Dietary fiber can bind to IQ in vitro, and a high-fat diet enhances the ability of rat liver microsomes to activate IQ. N-hydroxy-IQ can be esterified by O-acetyltransferase, sulfotransferase, and prolyl-tRNA synthetase, but at much lower rates than aromatic amines. N-acetylation of IQ may not be important for DNA binding. Human liver microsomes can activate IQ into a DNA-reactive substance. The isoenzyme involved in this process was initially identified as CYP IA2 (p450 IA2). Studies have shown that this enzyme is also responsible for the generation of N-hydroxy-IQ in hepatocyte cytosol. Human liver and colon cytosol can catalyze the conversion of N-hydroxylated IQ to its DNA-bound form, but N-acetylation was not observed under the same conditions. DNA-bound products were also found in human mammary epithelial cells cultured in a medium containing IQ. In human fetal liver tissue, cytochrome p450 HFLa is the major activating enzyme of IQ. Known human metabolites of 2-amino-3-methylimidazo[4,5-F]quinoline include N-hydroxy-2-amino-3-methylimidazo[4,5-F]quinoline (N-hydroxy-IQ).

Interactions
Methyl parathion and methyl paraoxonium enhance the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), while ethyl parathion does not. This synergistic mutagenic effect was observed in Salmonella typhimurium strain YG1024. Mammalian microsomal activation is essential for IQ to exert its synergistic mutagenic effect.

[1]. Carcinogenicity in mice of a mutagenic compound, 2-amino-3-methylimidazo4,5-fquinoline, from broiled sardine, cooked beef and beef extract. Carcinogenesis. 1984 Jul;5(7):921-4.

According to the International Agency for Research on Cancer (IARC) of the World Health Organization, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is carcinogenic. 2-Amino-3-methylimidazo[4,5-f]quinoline is a light brown crystalline solid or light brown powder. (NTP, 1992) 3-Methyl-3H-imidazo[4,5-f]quinoline-2-amine is an imidazoquinoline formed by replacing the methyl group at the 3-position and the amino group at the 2-position of 3H-imidazo[4,5-f]quinoline. It is a carcinogen. 2-Amino-3-methylimidazo[4,5-f]quinoline is a synthetic light brown crystalline solid, soluble in dimethyl sulfoxide and methanol. It is produced in small quantities for research purposes. 2-Amino-3-methylimidazo[4,5-f]quinoline is naturally formed during the cooking of muscle-based foods (meat and fish). The amount of this chemical produced depends on the cooking temperature, cooking time, and cooking method (directly or indirectly). 2-Amino-3-methylimidazo[4,5-f]quinoline is also found in processed food flavorings, beer, wine, and cigarette smoke. It is likely a human carcinogen. (NCI05)
A mutagen found in baked goods; RN refers to the parent compound; structure is found in the first reference; often abbreviated as IQ in the literature
Structure in the first reference

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Mechanism of Action
This study investigated the roles of oxidative stress, different types of DNA damage, and the expression of DNA repair enzymes in 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced colonic and hepatic mutations. Four groups of six Big Blue rats were fed diets containing 0, 20, 70, and 200 mg/kg IQ for three weeks. Results showed that DNA adducts (³²P-post-labeling) and DNA strand breaks (comet assay) in colonic and hepatic tissues were dose-dependent, with the highest levels of both in the colon. Dose-dependent mutation induction was observed in both the colon and liver; the same dose of IQ resulted in twice as many cII mutations in the liver as in the colon. The IQ-induced colonic mutation profile was not significantly different from that in the control group. The expression of ERCC1 and OGG1 in the colon was higher than in the liver and was unaffected by the IQ diet. Results regarding oxidative stress biomarkers remain inconclusive. The results indicated that DNA adducts, rather than oxidative stress, were the initiating factors for IQ-induced liver and colon cancer. The lower mutation frequency in the colon compared to the liver may be related to the higher expression of DNA repair enzymes in the colon. In spontaneously formed and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced small and colonic tumors in C57BL/6J-Min/... mice, the main mechanism of tumor induction was the deletion of the wild-type Apc allele, i.e., loss of heterozygosity (LOH). 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) inhibited LPS-induced expression of the iNOS (inducible nitric oxide synthase) gene in RAW 264.7 cells. The most likely mechanism explaining this biological effect involves the negative regulation of the NF-κB/Rel and p38 kinase pathways.
...The immunosuppression induced by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) may be related to PKC downregulation and subsequent inhibition of NF-κB and AP-1 activation, thereby affecting IL-2 gene expression.
For more complete data on the mechanisms of action of 2-amino-3-methylimidazo[4,5-f]quinoline (6 entries in total), please visit the HSDB record page.

C11H10N4

198.22

198.091

76180-96-6

77314-22-8;hydrobromide

53462

Crystalline solid

1.41 g/cm3

458.7ºC at 760 mmHg

greater than 572 °F (NTP, 1992) ; >300 °C ; 300 °C

231.2ºC

2.285

1

3

0

15

245

0

CN1C2=C(C3=C(C=C2)N=CC=C3)N=C1N

ARZWATDYIYAUTA-UHFFFAOYSA-N

InChI=1S/C11H10N4/c1-15-9-5-4-8-7(3-2-6-13-8)10(9)14-11(15)12/h2-6H,1H3,(H2,12,14)

3-methylimidazo[4,5-f]quinolin-2-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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.)