Target Information

Target General Infomation
Target ID
T14834
Former ID
TTDR00443
Target Name
Cytosolic phospholipase A2
Gene Name
PLA2G4A
Synonyms
CPLA2; Phospholipase A2 group IVA; PLA2G4A
Target Type
Discontinued
Disease Asthma [ICD10: J45]
Function
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.
BioChemical Class
Carboxylic ester hydrolase
Target Validation
T14834
UniProt ID
P47712
EC Number
EC 3.1.1.5
Sequence
MSFIDPYQHIIVEHQYSHKFTVVVLRATKVTKGAFGDMLDTPDPYVELFISTTPDSRKRT
RHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMDETLGTATFTVSSMKVGEKKEV
PFIFNQVTEMVLEMSLEVCSCPDLRFSMALCDQEKTFRQQRKEHIRESMKKLLGPKNSEG
LHSARDVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSH
PDFPEKGPEEINEELMKNVSHNPLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIG
ETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYG
TFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGVSGSQSRGSTMEEE
LENITTKHIVSNDSSDSDDESHEPKGTENEDAGSDYQSDNQASWIHRMIMALVSDSALFN
TREGRAGKVHNFMLGLNLNTSYPLSPLSDFATQDSFDDDELDAAVADPDEFERIYEPLDV
KSKKIHVVDSGLTFNLPYPLILRPQRGVDLIISFDFSARPSDSSPPFKELLLAEKWAKMN
KLPFPKIDPYVFDREGLKECYVFKPKNPDMEKDCPTIIHFVLANINFRKYRAPGVPRETE
EEKEIADFDIFDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRR
QNPSRCSVSLSNVEARRFFNKEFLSKPKA
Drugs and Mode of Action
Drug(s) EFIPLADIB Drug Info Terminated Asthma [529485]
Inhibitor (S)-Ethyl 6-(2-oxohexadecanamido)decanoate Drug Info [529795]
(S)-Methyl 4-(2-oxohexadecanamido)octanoate Drug Info [529795]
(S)-tert-Butyl 4-(2-oxohexadecanamido)pentanoate Drug Info [529795]
(Z)-1,1,1,2,2,3,3-heptafluorohenicos-12-en-4-one Drug Info [530831]
1,1,1,2,2,3,3,5-octafluoro-8-phenyloctan-4-one Drug Info [530831]
1,1,1,2,2,3,3-heptafluoro-8-phenyloctan-4-ol Drug Info [530831]
1,1,1,2,2,4-hexafluoro-7-phenylheptan-3-one Drug Info [530831]
1,1,1,2,2-Pentafluoro-8-phenyl-octan-3-one Drug Info [529843]
1,1,1,2,2-Pentafluoro-9-phenyl-nonan-3-one Drug Info [529843]
1,1,1,3-Tetrafluoro-6-phenylhexan-2-one Drug Info [530831]
1,1,1,3-Tetrafluoro-7-phenylheptan-2-one Drug Info [530831]
1,1,1,3-Tetrafluoro-heptadecan-2-one Drug Info [529843]
1,1,1-Trifluoro-4-(4-hexyloxy-phenyl)-butan-2-one Drug Info [529843]
1,1,1-Trifluoro-5-(4-octylphenoxy)pentan-2-one Drug Info [530831]
1,1,1-Trifluoro-6-(4-hexyloxy-phenyl)-hexan-2-one Drug Info [529843]
1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one Drug Info [530831]
1,1,1-Trifluoro-7-phenylheptan-2-one Drug Info [529843]
1,1,1-Trifluoro-8-phenyl-octan-2-one Drug Info [529843]
1,1,1-trifluoroheptadecan-2-one Drug Info [529843]
1-Imidazol-1-yl-3-(4-octylphenoxy)propan-2-one Drug Info [530576]
4-(2-oxohexadecanamido)butanoic acid Drug Info [528680]
4-(4-Decyloxy-phenyl)-1,1,1-trifluoro-butan-2-one Drug Info [529843]
6-(4-Decyloxy-phenyl)-1,1,1-trifluoro-hexan-2-one Drug Info [529843]
Allyl 4-(2-oxohexadecanamido)butanoate Drug Info [529795]
AR-C70484XX Drug Info [530576]
ARACHIDONYL TRIFLUOROMETHYLKETONE Drug Info [530576]
Arachidonyltrifluoromethyl ketone Drug Info [535403]
AX-006 Drug Info [530139]
AX-048 Drug Info [530139]
ECOPLADIB Drug Info [529940]
EFIPLADIB Drug Info [529940]
Ethyl 2-(2-oxohexadecanamido)acetate Drug Info [529795]
Ethyl 4-(2-oxohexadecanamido)benzoate Drug Info [529795]
Methyl 2-(2-oxo-8-phenyloctanamido)acetate Drug Info [529795]
Methyl 2-(2-oxohexadecanamido)acetate Drug Info [529795]
Methyl arachidonyl fluorophosphonate Drug Info [535403]
N-(4-Ethoxybutyl)-2-oxohexadecanamide Drug Info [529795]
Tert-Butyl 2-(2-oxohexadecanamido)acetate Drug Info [529795]
Tert-Butyl 3-(2-oxo-8-phenyloctanamido)propanoate Drug Info [529795]
Tert-Butyl 3-(2-oxohexadecanamido)propanoate Drug Info [529795]
Tert-Butyl 5-(2-oxohexadecanamido)pentanoate Drug Info [529795]
WAY-196025 Drug Info [529940]
[3,4''']biflavone Drug Info [529028]
[4',4''']-biflavone Drug Info [529028]
[6,3''']biflavone Drug Info [529028]
[6,4''']biflavone Drug Info [529028]
Pathways
BioCyc Pathway Phospholipases
KEGG Pathway Glycerophospholipid metabolism
Ether lipid metabolism
Arachidonic acid metabolism
Linoleic acid metabolism
alpha-Linolenic acid metabolism
Metabolic pathways
MAPK signaling pathway
Ras signaling pathway
Vascular smooth muscle contraction
VEGF signaling pathway
Platelet activation
Fc epsilon RI signaling pathway
Fc gamma R-mediated phagocytosis
Glutamatergic synapse
Serotonergic synapse
Long-term depression
Inflammatory mediator regulation of TRP channels
GnRH signaling pathway
Ovarian steroidogenesis
Oxytocin signaling pathway
Choline metabolism in cancer
NetPath Pathway TCR Signaling Pathway
PANTHER Pathway Angiogenesis
Endothelin signaling pathway
Inflammation mediated by chemokine and cytokine signaling pathway
Oxidative stress response
VEGF signaling pathway
CCKR signaling map ST
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells
Endothelins
PDGFR-beta signaling pathway
Signaling mediated by p38-alpha and p38-beta
PathWhiz Pathway Fc Epsilon Receptor I Signaling in Mast Cells
Reactome Acyl chain remodelling of PC
Acyl chain remodelling of PE
Acyl chain remodelling of PI
ADP signalling through P2Y purinoceptor 1
Platelet sensitization by LDL
WikiPathways Prostaglandin Synthesis and Regulation
p38 MAPK Signaling Pathway
Glycerophospholipid biosynthesis
Arachidonic acid metabolism
PDGF Pathway
Integrated Pancreatic Cancer Pathway
AGE/RAGE pathway
Opioid Signalling
Signal amplification
Platelet homeostasis
References
Ref 529485Indole cytosolic phospholipase A2 alpha inhibitors: discovery and in vitro and in vivo characterization of 4-{3-[5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoic acid, efipladib. J Med Chem. 2008 Jun 26;51(12):3388-413.
Ref 528680J Med Chem. 2007 Mar 22;50(6):1380-400. Epub 2007 Feb 17.Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha.
Ref 529028Bioorg Med Chem. 2007 Nov 15;15(22):7138-43. Epub 2007 Aug 22.Inhibitory effect of synthetic C-C biflavones on various phospholipase A(2)s activity.
Ref 529795Bioorg Med Chem. 2008 Dec 15;16(24):10257-69. Epub 2008 Nov 1.Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A(2)enzymes.
Ref 529843J Med Chem. 2008 Dec 25;51(24):8027-37.Synthesis of polyfluoro ketones for selective inhibition of human phospholipase A2 enzymes.
Ref 529940J Med Chem. 2009 Feb 26;52(4):1156-71.Reactions of functionalized sulfonamides: application to lowering the lipophilicity of cytosolic phospholipase A2alpha inhibitors.
Ref 530139Bioorg Med Chem. 2009 Jul 1;17(13):4833-43. Epub 2009 May 3.2-Oxoamide inhibitors of phospholipase A2 activity and cellular arachidonate release based on dipeptides and pseudodipeptides.
Ref 530576Bioorg Med Chem. 2010 Jan 15;18(2):945-52. Epub 2009 Nov 17.1-Indol-1-yl-propan-2-ones and related heterocyclic compounds as dual inhibitors of cytosolic phospholipase A(2)alpha and fatty acid amidehydrolase.
Ref 530831J Med Chem. 2010 May 13;53(9):3602-10.Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2.
Ref 53540385-kDa cPLA(2) plays a critical role in PPAR-mediated gene transcription in human hepatoma cells. Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G586-97.

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