Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.1.1.7 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 .
    View publication on PubMed
Search for more literature for 3.1.1.7

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 superposition of model complexes between cyclosarin-AChE conjugate (from PDB ID 5FPP) and oxime 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)propane dibromide, 4-carbamoyl-1-(3-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium dibromide, and 4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium dibromide 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 dibromide 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 AChE, 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 (BChE, EC 3.1.1.8) 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 dibromide, 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane dibromide, and (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene dibromide 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 VX Homo sapiens
pralidoxime
-
 Homo sapiens
sarin
-
 Homo sapiens
Tabun i.e. N,N-dimethylamido-O-ethyl cyanophosphate, superposition of model complexes between tabun-AChE conjugate (from PDB IDs 2JEZ, 3DL4, and 2JF0) and oxime 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)propane dibromide, 4-carbamoyl-1-(3-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium dibromide, and 4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium dibromide Homo sapiens
trimedoxime
-
 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
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
 Homo sapiens
-
SH-SY5Y cell neuroblastoma-derived cell line Homo sapiens
-

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
AChE
-
 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
0.012
-
 4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)butyl)pyridinium pH 7.4, 25°C Homo sapiens
0.021
-
 4-carbamoyl-1-(4-(3,5-dichloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium pH 7.4, 25°C Homo sapiens
0.022
-
 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
0.024
-
 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
0.025
-
 asoxime pH 7.4, 25°C Homo sapiens
0.036
-
 4-carbamoyl-1-(4-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)butyl)pyridinium pH 7.4, 25°C Homo sapiens
0.042
-
 4-carbamoyl-1-(3-(3-chloro-4-[(hydroxyimino)methyl]-pyridinium-1-yl)propyl)pyridinium pH 7.4, 25°C Homo sapiens
0.18
-
 pralidoxime pH 7.4, 25°C Homo sapiens