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Literature summary extracted from

  • Tarui, M.; Shindou, H.; Kumagai, K.; Morimoto, R.; Harayama, T.; Hashidate, T.; Kojima, H.; Okabe, T.; Nagano, T.; Nagase, T.; Shimizu, T.
    Selective inhibitors of a PAF biosynthetic enzyme lysophosphatidylcholine acyltransferase 2 (2014), J. Lipid Res., 55, 1386-1396.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.3.1.67 analysis procedure for identification of LPCAT2-specific inhibitors via high-throughput screening Mus musculus
2.3.1.67 analysis procedure for identification of LPCAT2-specific inhibitors via high-throughput screening Homo sapiens
2.3.1.67 drug development identification of LPCAT2-specific inhibitors in order to ameliorate PAF-related inflammatory diseases, fluorescence-based high-throughput library screening Mus musculus
2.3.1.67 drug development identification of LPCAT2-specific inhibitors in order to ameliorate PAF-related inflammatory diseases, fluorescence-based high-throughput library screening Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.67 expression in CHO-S and CHO-S-PAFR cells Homo sapiens
2.3.1.67 gene LPCAT2, recombinant expression of FLAG-tagged human LPCAT2 in CHO cells Homo sapiens
2.3.1.67 gene LPCAT2, recombinant expression of FLAG-tagged mouse LPCAT2 in CHO cells, stable recombinant enzyme expression in RAW264.7 cells Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.67 3,4-dichloro-1-(4,5-dichloro-2-methoxyphenyl)-1H-pyrrole-2,5-dione
-
 Homo sapiens
2.3.1.67 3,4-dichloro-1-(4,5-dichloro-2-methoxyphenyl)-1H-pyrrole-2,5-dione
-
 Mus musculus
2.3.1.67 3-chloro-1-(3-chloro-4-methoxyphenyl)-4-(2-methoxyphenoxy)-1H-pyrrole-2,5-dione
-
 Homo sapiens
2.3.1.67 3-chloro-1-(3-chloro-4-methoxyphenyl)-4-(2-methoxyphenoxy)-1H-pyrrole-2,5-dione
-
 Mus musculus
2.3.1.67 3-chloro-1-(4,5-dichloro-2-methoxyphenyl)-4-(2-hydroxyanilino)-1H-pyrrole-2,5-dione
-
 Homo sapiens
2.3.1.67 3-chloro-1-(4,5-dichloro-2-methoxyphenyl)-4-(2-hydroxyanilino)-1H-pyrrole-2,5-dione
-
 Mus musculus
2.3.1.67 3-chloro-4-(morpholin-4-yl)-1-(4-phenoxyphenyl)-1H-pyrrole-2,5-dione
-
 Homo sapiens
2.3.1.67 3-chloro-4-(morpholin-4-yl)-1-(4-phenoxyphenyl)-1H-pyrrole-2,5-dione
-
 Mus musculus
2.3.1.67 butyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate 80.4% inhibition at 0.02 mM Homo sapiens
2.3.1.67 butyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate 83.0% inhibition at 0.02 mM Mus musculus
2.3.1.67 methyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate
-
 Homo sapiens
2.3.1.67 methyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate
-
 Mus musculus
2.3.1.67 methyl 4-[3-chloro-2,5-dioxo-4-(4-sulfamoylanilino)-2,5-dihydro-1H-pyrrol-1-yl]benzoate
-
 Homo sapiens
2.3.1.67 methyl 4-[3-chloro-2,5-dioxo-4-(4-sulfamoylanilino)-2,5-dihydro-1H-pyrrol-1-yl]benzoate
-
 Mus musculus
2.3.1.67 additional information identification of LPCAT2-specific inhibitors in order to ameliorate platelet-activating factor-related inflammatory diseases: N-phenylmaleimide derivatives are selected from a 174000-compound library using fluorescence-based high-throughput screening followed by the evaluation of the effects on LPCAT1 and LPCAT2 activities, cell viability, and cellular platelet-activating factor production. The selected compounds have low inhibitory effects on enzyme LPCAT1 activity which is mostly expressed in the lungs where it produces platelet-activating factor, indicating that adverse effects on respiratory functions may be avoided. Structure-activity relationship, overview Homo sapiens
2.3.1.67 additional information identification of LPCAT2-specific inhibitors in order to ameliorate platelet-activating factor-related infl ammatory diseases: N-phenylmaleimide derivatives are selected from a 174000-compound library using fluorescence-based high-throughput screening followed by the evaluation of the effects on LPCAT1 and LPCAT2 activities, cell viability, and cellular platelet-activating factor production. The selected compounds have low inhibitory effects on enzyme LPCAT1 activity which is mostly expressed in the lungs where it produces platelet-activating factor, indicating that adverse effects on respiratory functions may be avoided. Structure-activity relationship, overview Mus musculus
2.3.1.67 propan-2-yl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate 95.2% inhibition at 0.02 mM Homo sapiens
2.3.1.67 propan-2-yl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate 95.5% inhibition at 0.02 mM Mus musculus
2.3.1.67 propan-2-yl 4-(3-chloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate competitively inhibits the lyso-PAFAT activity with acetyl-CoA Homo sapiens
2.3.1.67 propan-2-yl 4-(3-chloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate compound competes with acetyl-CoA for the inhibition of isoform LPCAT2 lyso-PAFAT activity and suppresses platelet-activating factor biosynthesis in mouse peritoneal macrophages stimulated with a calcium ionophore. The compound has low inhibitory effects on isoform LPCAT1 activity Mus musculus
2.3.1.67 propan-2-yl 4-[3-chloro-4-(2-hydroxyanilino)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]benzoate 83.1% inhibition at 0.02 mM Homo sapiens
2.3.1.67 propan-2-yl 4-[3-chloro-4-(2-hydroxyanilino)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]benzoate 82.4% inhibition at 0.02 mM Mus musculus
2.3.1.67 propan-2-yl 4-[3-chloro-4-(morpholin-4-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]benzoate
-
 Homo sapiens
2.3.1.67 propan-2-yl 4-[3-chloro-4-(morpholin-4-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]benzoate
-
 Mus musculus
2.3.1.67 propyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate 85.4% inhibition at 0.02 mM Homo sapiens
2.3.1.67 propyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate 86.7% inhibition at 0.02 mM Mus musculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.1.67 microsome
-
 Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.67 acetyl-CoA + 1-alkyl-sn-glycero-3-phosphocholine Mus musculus
-
 CoA + 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine
-
 ?
2.3.1.67 acetyl-CoA + 1-alkyl-sn-glycero-3-phosphocholine Homo sapiens
-
 CoA + 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.67 Homo sapiens Q7L5N7
-
-
2.3.1.67 Homo sapiens Q7L5N7 gene Lpcat2
-
2.3.1.67 Mus musculus Q8BYI6
-
-
2.3.1.67 Mus musculus Q8BYI6 gene Lpcat2
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.1.67 macrophage
-
 Mus musculus
-
2.3.1.67 macrophage
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.67 acetyl-CoA + 1-alkyl-sn-glycero-3-phosphocholine
-
 Mus musculus CoA + 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine
-
 ?
2.3.1.67 acetyl-CoA + 1-alkyl-sn-glycero-3-phosphocholine
-
 Homo sapiens CoA + 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine
-
 ?
2.3.1.67 acetyl-CoA + 1-alkyl-sn-glycero-3-phosphocholine substrates are d31-16:0 LPC or d4-lyso-PAF Mus musculus CoA + 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine
-
 ?
2.3.1.67 acetyl-CoA + 1-alkyl-sn-glycero-3-phosphocholine substrates are d31-16:0 LPC or d4-lyso-PAF Homo sapiens CoA + 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.67 acetyl-CoA:lyso-PAF acetyltransferase
-
 Mus musculus
2.3.1.67 acetyl-CoA:lyso-PAF acetyltransferase
-
 Homo sapiens
2.3.1.67 LPCAT2
-
 Mus musculus
2.3.1.67 LPCAT2
-
 Homo sapiens
2.3.1.67 lyso-PAFAT
-
 Mus musculus
2.3.1.67 lyso-PAFAT
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.67 37
-
 assay at Mus musculus
2.3.1.67 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.67 7.4
-
 assay at Mus musculus
2.3.1.67 7.4
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.1.67 acetyl-CoA
-
 Mus musculus
2.3.1.67 acetyl-CoA
-
 Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.1.67 0.0003
-
 pH 7.4, 37°C Homo sapiens propyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate
2.3.1.67 0.00033
-
 pH 7.4, 37°C Homo sapiens butyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate
2.3.1.67 0.00047
-
 pH 7.4, 37°C Homo sapiens propan-2-yl 4-(3-chloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate
2.3.1.67 0.00116
-
 pH 7.4, 37°C Homo sapiens 3-chloro-4-(morpholin-4-yl)-1-(4-phenoxyphenyl)-1H-pyrrole-2,5-dione
2.3.1.67 0.00127
-
 pH 7.4, 37°C Homo sapiens propan-2-yl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate
2.3.1.67 0.00758
-
 pH 7.4, 37°C Homo sapiens 3-chloro-1-(3-chloro-4-methoxyphenyl)-4-(2-methoxyphenoxy)-1H-pyrrole-2,5-dione
2.3.1.67 0.0116
-
 pH 7.4, 37°C Homo sapiens methyl 4-(3,4-dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoate
2.3.1.67 0.0133
-
 pH 7.4, 37°C Homo sapiens propan-2-yl 4-[3-chloro-4-(2-hydroxyanilino)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]benzoate
2.3.1.67 0.0171
-
 pH 7.4, 37°C Homo sapiens 3,4-dichloro-1-(4,5-dichloro-2-methoxyphenyl)-1H-pyrrole-2,5-dione
2.3.1.67 0.02
-
 pH 7.4, 37°C Homo sapiens 3-chloro-1-(4,5-dichloro-2-methoxyphenyl)-4-(2-hydroxyanilino)-1H-pyrrole-2,5-dione
2.3.1.67 0.02
-
 pH 7.4, 37°C Homo sapiens propan-2-yl 4-[3-chloro-4-(morpholin-4-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]benzoate
2.3.1.67 0.02
-
 pH 7.4, 37°C Homo sapiens methyl 4-[3-chloro-2,5-dioxo-4-(4-sulfamoylanilino)-2,5-dihydro-1H-pyrrol-1-yl]benzoate

Expression

EC Number Organism Comment Expression
2.3.1.67 Mus musculus under inflammatory conditions, LPCAT2, but not LPCAT1, is activated and upregulated to produce the platelet-activating factor up
2.3.1.67 Homo sapiens under inflammatory conditions, LPCAT2, but not LPCAT1, is activated and upregulated to produce the platelet-activating factor up

General Information

EC Number General Information Comment Organism
2.3.1.67 evolution two entities of lyso-PAFAT belonging to the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family: a constitutively expressed lyso-PAFAT, LPCAT1,and an inducible lyso-PAFAT, LPCAT2. LPCAT1 is mainly expressed in the lungs and produces PAF and dipalmitoyl-phosphatidylcholine, which is a main component of a pulmonary surfactant essential for respiration. LPCAT2 is mainly expressed in inflammatory cells and also possesses biosynthetic activities for PAF and cellular membrane phosphatidylcholine Mus musculus
2.3.1.67 evolution two entities of lyso-PAFAT belonging to the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family: a constitutively expressed lyso-PAFAT, LPCAT1,and an inducible lyso-PAFAT, LPCAT2. LPCAT1 is mainly expressed in the lungs and produces PAF and dipalmitoyl-phosphatidylcholine, which is a main component of a pulmonary surfactant essential for respiration. LPCAT2 is mainly expressed in inflammatory cells and also possesses biosynthetic activities for PAF and cellular membrane phosphatidylcholine Homo sapiens
2.3.1.67 metabolism following extracellular stimulation, platelet-activating factor is rapidly biosynthesized via a remodeling pathway in inflammatory cells such as macrophages and neutrophils. In the remodeling pathway, one of the membrane phospholipids, 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine is hydrolyzed by phospholipase A2 to produce free fatty acids and lyso-PAF (1-O-alkyl-2-hydroxy-sn-glycero-3-phosphocholine). Acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAFAT) subsequently converts lyso-PAF to PAF, which is rapidly degraded to lyso-PAF and acetic acid by PAF acetylhydrolases, terminating its effects Mus musculus
2.3.1.67 metabolism following extracellular stimulation, platelet-activating factor is rapidly biosynthesized via a remodeling pathway in inflammatory cells such as macrophages and neutrophils. In the remodeling pathway, one of the membrane phospholipids, 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine is hydrolyzed by phospholipase A2 to produce free fatty acids and lyso-PAF (1-O-alkyl-2-hydroxy-sn-glycero-3-phosphocholine). Acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAFAT) subsequently converts lyso-PAF to PAF, which is rapidly degraded to lyso-PAF and acetic acid by PAF acetylhydrolases, terminating its effects Homo sapiens
2.3.1.67 physiological function platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid mediator. In response to extracellular stimuli, PAF is rapidly biosynthesized by lyso-PAF acetyltransferase. Under inflammatory conditions, LPCAT2, but not LPCAT1, is activated and upregulated to produce the platelet-activating factor Mus musculus
2.3.1.67 physiological function platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid mediator. In response to extracellular stimuli, PAF is rapidly biosynthesized by lyso-PAF acetyltransferase. Under inflammatory conditions, LPCAT2, but not LPCAT1, is activated and upregulated to produce the platelet-activating factor Homo sapiens