Literature summary for 3.1.1.8 extracted from

Zorbaz, T.; Malinak, D.; Marakovic, N.; Macek Hrvat, N.; Zandona, A.; Novotny, M.; Skarka, A.; Andrys, R.; Benkova, M.; Soukup, O.; Katalinic, M.; Kuca, K.; Kovarik, Z.; Musilek, K.
Pyridinium oximes with ortho-positioned chlorine moiety exhibit improved physicochemical properties and efficient reactivation of human acetylcholinesterase inhibited by several nerve agents (2018), J. Med. Chem., 61, 10753-10766 .

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Inhibitors

Inhibitors	Comment	Organism	Structure
(E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene	-	Homo sapiens
1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane	-	Homo sapiens
1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)propane	-	Homo sapiens
4-carbamoyl-1-(3-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium	-	Homo sapiens
4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)butyl)pyridinium	-	Homo sapiens
4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium	-	Homo sapiens
4-carbamoyl-1-(4-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)butyl)pyridinium	-	Homo sapiens
4-carbamoyl-1-[(2E)-4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)but-2-en-1-yl]pyridinium	-	Homo sapiens
4-carbamoyl-1-[(2E)-4-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)but-2-en-1-yl]pyridinium	-	Homo sapiens
asoxime	-	Homo sapiens
cyclosarin	-	Homo sapiens
additional information	pyridinium oximes with ortho-positioned chlorine moiety provide efficient reactivation of human acetylcholinesterase inhibited by several nerve agents, overview. The most potent is the dichlorinated analogue of oxime 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)propane with significantly improved ability to reactivate the conjugated enzyme due to improved binding affinity and molecular recognition. Among the standard oximes, trimedoxime (TMB-4) is the superior reactivator of tabun-inhibited acetylcholinesterase (AChE, EC 3.1.1.7), but it is also the most toxic, which prevents its use in therapy, while asoxime (HI-6) has no reactivation potency (below 20%). Reversible inhibition of recombinant human AChE and purified human plasma butyrylcholinesterase with oximes. The parent compounds and the commercial standards pralidoxime and asoxime are predicted to have minimal CNS penetrability. 1-(4-Hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)propane, 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane, and (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene oximes show low cytotoxic potential in different cell lines, fibroblasts and hepatic, kidney, blood, and ovary cells	Homo sapiens
O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonothioate	nerve agent VX	Homo sapiens
pralidoxime	-	Homo sapiens
sarin	-	Homo sapiens
Tabun	i.e. N,N-dimethylamido-O-ethyl cyanophosphate	Homo sapiens
trimedoxime	-	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P06276	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
blood plasma	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
butyrylcholine + H2O	-	Homo sapiens	choline + butyrate	-	?
butyrylthiocholine + H2O	substrate is butyrylthiocholine iodide, activity detection using 5,5'-dithio-bis(2-nitrobenzoic acid) colorimetric assay and measurement of the absorbance at 412 nm	Homo sapiens	thiocholine + butyrate	-	?

Synonyms

Synonyms	Comment	Organism
BChE	-	Homo sapiens
butyrylcholinesterase	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	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
0.14	-	4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)butyl)pyridinium	pH 7.4, 25°C	Homo sapiens
0.187	-	4-carbamoyl-1-[(2E)-4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)but-2-en-1-yl]pyridinium	pH 7.4, 25°C	Homo sapiens
0.195	-	4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium	pH 7.4, 25°C	Homo sapiens
0.215	-	asoxime	pH 7.4, 25°C	Homo sapiens
0.265	-	4-carbamoyl-1-(4-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)butyl)pyridinium	pH 7.4, 25°C	Homo sapiens
0.273	-	4-carbamoyl-1-(3-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium	pH 7.4, 25°C	Homo sapiens
0.294	-	4-carbamoyl-1-[(2E)-4-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)but-2-en-1-yl]pyridinium	pH 7.4, 25°C	Homo sapiens
0.39	-	pralidoxime	pH 7.4, 25°C	Homo sapiens

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Release 2023.1 (January 2023)