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Chemical Compound Review:

Acetamidin ethanimidamide

Synonyms: Acetamidine, Acetamidinium, acetimidamide, Ethanimidamide, AGN-PC-0D8GHT, ...

Miller, A.A. et al., Mancinelli, R. et al., McDonald, M. et al., Payne, C.M. et al., Young, R.J. et al., et al.

Anniyappan, Talawar, Gore, Venugopalan, Gandhe, Young, Beams, Carter, Clark, Coe, Chambers, Davies, Dawson, Drysdale, Franzman, French, Hodgson, Hodson, Kleanthous, Rider, Sanders, Sawyer, Scott, Shearer, Stocker, Smith, Tackley, Knowles,

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High impact information on acetamidine

The affinity of h.u. kallikrein for acetamidine and ethylamine changes about 5-fold with pH between pH 5 and 3 [1].
The preference of the various enzymes for the guanidinium or ammonium group in reflected by the different promotor effect that acetamidine or ethylamine has on the catalyzed hydrolysis of neutral substrates [2].
Both the selective iNOS inhibitor, N-(3-(Aminomethyl) benzyl) acetamidine dihydrochloride (1400W; 10(-6) M) and the superoxide dismutase mimetic, Mn [III] tetrakis [1-methyl-4-pyridyl] porphyrin, (MnTMPyP; 10(-4) M) reversed the hyperesponsiveness (pD(2) values, 1400W, 5.9+/-0.1; MnTMPyP, 5.81+/-0.1, P<0.05) [3].
Using an isotonic - non-isovolumic technique, peristaltic activity and video images of the external wall of colonic segments were recorded before and after addition to the medium of Aminoguanidine (AG) and N-(3-(aminomethyl)benzyl) acetamidine (W1400) [10(-7) M-10(-4) M], two iNOS inhibitors [4].
As an initial case study, the potent isoform selective inhibitor N-(3-(aminomethyl)benzyl) acetamidine (1400W) of inducible nitric oxide synthase (iNOS) has been conjugated to a caging molecule 6-bromo-7-hydroxy-4-hydroxyquinoline-2-ylmethyl acetyl ester (Bhc) [5].

Biological context of acetamidine

In the present study, 1,1-diamino-2,2-dinitroethylene has been synthesised by treatment of acetamidinium chloride with diethylmalonate to obtain 2-methyl-pyrimidine-4,6-dione which on nitration followed by hydrolysis gave FOX-7 [6].
To accomplish this, we treated HepG2 cell lines that were individually transfected with 13 different promoter/response element (RE) chloramphenicol acetyl transferase (CAT) reporter constructs, with a highly selective NOS2 inhibitor, 1400W [N-(3-(aminomethyl)benzyl) acetamidine)] [7].

Anatomical context of acetamidine

This study examines the effects of combination therapy with the nitric oxide (NO) donor S-nitroso-N-acetylcysteine (SNAC) and the iNOS inhibitor N-(3-(aminomethyl)benzyl) acetamidine (1400W) on contractile function in reperfused rat skeletal muscle [8].

Associations of acetamidine with other chemical compounds

The synthesis and in vitro evaluation of the acetamidine derivatives of hetero-substituted lysine and homolysine analogues have identified potent inhibitors of human nitric oxide synthase enzymes, including examples with marked selectivity for the inducible isoform [9].
A comparison was made between NAC and the N-[3-(aminomethyl)benzyl] acetamidine (1400W), an inhibitor of the inducible NO synthase (iNOS) [10].

Analytical, diagnostic and therapeutic context of acetamidine

Selective inhibition of iNOS activity with N-(3-(aminomethyl)benzyl) acetamidine (1400 W, 10 mg kg(-1) i.v., 5 min prior to the onset of resuscitation), also attenuated nitrotyrosine formation, renal dysfunction, liver injury and brain or muscular injury associated with haemorrhagic shock [11].

References

Catalytic properties of human urinary kallikrein. Antonini, E., Ascenzi, P., Menegatti, E., Bortolotti, F., Guarneri, M. Biochemistry (1982) [Pubmed]
Catalytic properties of serine proteases. 2. Comparison between human urinary kallikrein and human urokinase, bovine beta-trypsin, bovine thrombin, and bovine alpha-chymotrypsin. Ascenzi, P., Menegatti, E., Guarneri, M., Bortolotti, F., Antonini, E. Biochemistry (1982) [Pubmed]
Inducible nitric oxide synthase-derived superoxide contributes to hypereactivity in small mesenteric arteries from a rat model of chronic heart failure. Miller, A.A., Megson, I.L., Gray, G.A. Br. J. Pharmacol. (2000) [Pubmed]
Functional role of inducible nitric oxide synthase on mouse colonic motility. Mancinelli, R., Fabrizi, A., Vargiu, R., Morrone, L., Bagetta, G., Azzena, G.B. Neurosci. Lett. (2001) [Pubmed]
Photocontrol of nitric oxide production in cell culture using a caged isoform selective inhibitor. Perdicakis, B., Montgomery, H.J., Abbott, G.L., Fishlock, D., Lajoie, G.A., Guillemette, J.G., Jervis, E. Bioorg. Med. Chem. (2005) [Pubmed]
Synthesis, characterization and thermolysis of 1,1-diamino-2,2-dinitroethylene (FOX-7) and its salts. Anniyappan, M., Talawar, M.B., Gore, G.M., Venugopalan, S., Gandhe, B.R. J. Hazard. Mater. (2006) [Pubmed]
The specific NOS2 inhibitor, 1400W, sensitizes HepG2 cells to genotoxic, oxidative, xenobiotic, and endoplasmic reticulum stresses. Payne, C.M., Bernstein, H., Bernstein, C., Kunke, K., Garewal, H. Antioxid. Redox Signal. (2001) [Pubmed]
Addition of nitric oxide donor S-nitroso-N-acetylcysteine to selective iNOS inhibitor 1400W further improves contractile function in reperfused skeletal muscle. Barker, J.U., Qi, W.N., Cai, Y., Urbaniak, J.R., Chen, L.E. Microsurgery. (2005) [Pubmed]
Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine. Young, R.J., Beams, R.M., Carter, K., Clark, H.A., Coe, D.M., Chambers, C.L., Davies, P.I., Dawson, J., Drysdale, M.J., Franzman, K.W., French, C., Hodgson, S.T., Hodson, H.F., Kleanthous, S., Rider, P., Sanders, D., Sawyer, D.A., Scott, K.J., Shearer, B.G., Stocker, R., Smith, S., Tackley, M.C., Knowles, R.G. Bioorg. Med. Chem. Lett. (2000) [Pubmed]
N-Acetylcysteine negatively modulates nitric oxide production in endotoxin-treated rats through inhibition of NF-kappaB activation. Rota, C., Bergamini, S., Daneri, F., Tomasi, A., Virgili, F., Iannone, A. Antioxid. Redox Signal. (2002) [Pubmed]
Tyrphostin reduces the organ injury in haemorrhagic shock: role of inducible nitric oxide synthase. McDonald, M., Abdelrahman, M., Cuzzocrea, S., Thiemermann, C. Resuscitation. (2003) [Pubmed]

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