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Literature summary for 3.1.1.7 extracted from

  • Horn, G.; de Koning, M.C.; van Grol, M.; Thiermann, H.; Worek, F.
    Interactions between acetylcholinesterase, toxic organophosphorus compounds and a short series of structurally related non-oxime reactivators analysis of reactivation and inhibition kinetics in vitro (2018), Toxicol. Lett., 299, 218-225 .
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
additional information poisoning by organophosphorus compounds (OP) is characterized by inhibition of the key enzyme acetylcholinesterase (AChE) and potentially fatal outcomes in humans. Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiates synthesis of non-oxime reactivators, 4-amino-2-[(dimethylamino)methyl]phenol, 4-amino-2-((dimethylamino)methyl)phenol, and 4-amino-2-[[ethyl(methyl)amino]methyl]phenol, basing on the common structure 4-amino-2-((diethylamino)methyl)phenol (ADOC). 10 to 34Fold reactivation potency of compound 4-amino-2-[[ethyl(methyl)amino]methyl]phenol compared to 4-amino-2-((diethylamino)methyl)phenol mainly due to improved affinity, analysis of reactivation and inhibition kinetics in vitro, method. A combination of 4-amino-2-[[ethyl(methyl)amino]methyl]phenol and the bispyridinium oxime HI-6 is tested to reactivate OP-inhibited AChE, the superior reactivator of the respective OP-AChE combination dominates the reactivation process and a synergistic effect cannot be observed. Michaelis reactivation kinetics, Kr, and pseudo-first-order rate constant kobs, overview Homo sapiens

Application

Application Comment Organism
pharmacology poisoning by organophosphorus compounds (OP) is characterized by inhibition of the key enzyme acetylcholinesterase (AChE) and potentially fatal outcomes in humans. Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiates synthesis of non-oxime reactivators basing on the common structure 4-amino-2-((diethylamino)methyl)phenol (ADOC). 10 to 34Fold reactivation potency of compound 4-amino-2-[[ethyl(methyl)amino]methyl]phenol compared to 4-amino-2-((diethylamino)methyl)phenol mainly due to improved affinity Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
cyclosarin cyclohexylmethylphosphonofluoridate, GF Homo sapiens
additional information interactions between acetylcholinesterase, toxic organophosphorus compounds and a short series of structurally related non-oxime reactivators, analysis of reactivation and inhibition kinetics in vitro, overview. A combination of 4-amino-2-[[ethyl(methyl)amino]methyl]phenol and the bispyridinium oxime HI-6 is tested to reactivate OP-inhibited AChE, the superior reactivator of the respective OP-AChE combination dominates the reactivation process and a synergistic effect cannot be observed Homo sapiens
O-ethyl-S-[2-(diisopropylamino)-ethyl]-methylphosphonothioate VX Homo sapiens
paraoxonethyl diethyl-O-4-nitrophenylphosphate, paraoxon, PXE Homo sapiens
sarin isopropylmethylphosphonofluoridate, GB Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
acetylcholine + H2O Homo sapiens
-
choline + acetate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P22303
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information interactions between acetylcholinesterase, toxic organophosphorus compounds and a short series of structurally related non-oxime reactivators, analysis of reactivation and inhibition kinetics in vitro, overview Homo sapiens ?
-
?
acetylcholine + H2O
-
Homo sapiens choline + acetate
-
?
acetylthiocholine + H2O
-
Homo sapiens thiocholine + acetate
-
?

Synonyms

Synonyms Comment Organism
AChE
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics, KD, and Michaelis reactivation kinetics, Kr, and pseudo-first-order rate constant kobs Homo sapiens