Disease relevance of 112288-03-6

• Our studies demonstrated that, in rats and mice, 2MI induces thyroid hyperplasia and hypertrophy, and both 2MI and 4MI induce anemia; 2MI induces thyroid follicular-cell adenoma in male rats [1].
• Epididymal sperm granuloma induced by chronic administration of 2-methylimidazole in B6C3F1 mice [2].
• Groups of five male and five female rats and mice were fed diets containing 0, 1,200, 3,300, or 10,000 ppm 2-methylimidazole (equivalent to average daily doses of approximately 115, 290, or 770 mg 2-methylimidazole/ kg body weight to rats; 220, 640, or 2,100 mg/kg to male mice; 300, 800, or 2,400 to female mice) for 15 days [3].
• In rats, 2-methylimidazole induced a transient erythrocytosis in females and a minimal, exposure concentration-related, microcytic, normochromic, nonresponsive anemia [3].
• NTP technical report on the toxicity studies of 2- and 4-Methylimidazole (CAS No. 693-98-1 and 822-36-6) administered in feed to F344/N rats and B6C3F1 mice [3].

High impact information on 112288-03-6

• The addition of 2-methylimidazole chemically reconstituted the two-electron hydroperoxide reduction activity of H193A and abolished the cyclooxygenase lag phase [4].
• We report kinetics of CO rebinding to microperoxidase (MP) and 2-methylimidazole ligated Fe protoporphyrin IX in the 10 ns to 10 ms time window [5].
• The dissociation constants for binding of benzimidazole, imidazole, 2-ethylimidazole, 1-methylimidazole, 2-methylimidazole, and 1,2-dimethylimidazole to W191G were respectively 2.58, 0.70, 0.36, 0.057, 0.047, and 0.027 mM at pH 6 [6].
• In the 15-day studies, 2MI induced thyroid follicular-cell hyperplasia and pituitary pars-distalis hypertrophy in rats and thyroid follicular-cell hypertrophy and spleen hematopoietic-cell proliferation in mice; 4MI induced no histopathological changes in rats and mice [1].
• Two-year mouse and rat bioassay studies of 2-methylimidazole (2-MI) conducted by the National Toxicology Program revealed that epididymal sperm granuloma(SG)s occurred only in male B6C3F1 mice in a dose-related manner [2].

Chemical compound and disease context of 112288-03-6

• To confirm this, we searched for the imidazolone-related metabolite in rats after intravenous dosing of 2-methylimidazole (2MI; 14C-labeled and unlabeled form, 3 and 300 micromol/kg body weight) as a model compound [7].

Biological context of 112288-03-6

• The toxicokinetics of 2-methylimidazole (2-MI) were studied in male and female Fischer 344 rats after a single iv dose of 10 mg/kg or gavage dose of 25, 50, or 100 mg/kg [8].
• Substituting a 2-methylimidazole for the N-terminal amine and adding a benzylic alpha-methyl group with R stereochemistry to the rigidifying element produces even more potent inhibitors (IC50 = 20-50 nM) that are up to 500-fold selective for the fungal compared to human enzyme [9].
• Biomimetic oxidation of 2-methylimidazole derivative with a chemical model system for cytochrome P-450 [10].
• Imidazole derivatives, 1-methylimidazole and 2-methylimidazole, given intraperitoneally, blocked the effect of PGE1 on intraocular pressure and aqueous humor protein [11].

Anatomical context of 112288-03-6

• However, in the 14-week study of 2-methylimidazole, a significant exposure-related increase in the frequency of micronucleated normochromatic erythrocytes was noted in peripheral blood of male and female mice [3].
• When administered by intraperitoneal injection three times at 24-hour intervals, 2-methylimidazole produced negative results in bone marrow micronucleus tests in rats and mice [3].

Associations of 112288-03-6 with other chemical compounds

• A chemical model system for cytochrome P-450, consisting of tetraphenylporphyrin manganese chloride (TPPMnCl) and iodosylbenzene, efficiently oxidized 2-methylimidazole to 2-methylimidazolone [10].

Gene context of 112288-03-6

• Testing of 2-methylimidazole in vivo for induction of chromosomal damage, as measured by micronucleated erythrocyte frequency, produced mixed results [3].

Analytical, diagnostic and therapeutic context of 112288-03-6

• The spectroscopic information obtained for Fe(II)PP(OH-), Fe(II)PP(H2O), and Fe(II)PP(OH-)2 was compared with that previously reported for the 2-methylimidazole and 2-methylimidazolate complexes of Fe(II)PP, representative of the most common axial ligation in HS heme proteins [12].
• Visible and near infrared magnetic circular dichroism (MCD) spectra of heme proteins and enzymes as well as those of a protein-free heme bound to 2-methylimidazole were recorded and compared at 4.2 K in unrelaxed metastable and relaxed equilibrium heme stereochemistry [13].

References