Target Information
| Target General Information | Top | |||||
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| Target ID |
T14834
(Former ID: TTDR00443)
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| Target Name |
Cytosolic phospholipase A2 (GIVA cPLA2)
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| Synonyms |
Phospholipase A2 group IVA; PLA2G4; CPLA2
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| Gene Name |
PLA2G4A
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Atopic eczema [ICD-11: EA80] | |||||
| Function |
Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response. Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid.
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| BioChemical Class |
Carboxylic ester hydrolase
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| UniProt ID | ||||||
| Sequence |
MSFIDPYQHIIVEHQYSHKFTVVVLRATKVTKGAFGDMLDTPDPYVELFISTTPDSRKRT
RHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMDETLGTATFTVSSMKVGEKKEV PFIFNQVTEMVLEMSLEVCSCPDLRFSMALCDQEKTFRQQRKEHIRESMKKLLGPKNSEG LHSARDVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSH PDFPEKGPEEINEELMKNVSHNPLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIG ETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYG TFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGVSGSQSRGSTMEEE LENITTKHIVSNDSSDSDDESHEPKGTENEDAGSDYQSDNQASWIHRMIMALVSDSALFN TREGRAGKVHNFMLGLNLNTSYPLSPLSDFATQDSFDDDELDAAVADPDEFERIYEPLDV KSKKIHVVDSGLTFNLPYPLILRPQRGVDLIISFDFSARPSDSSPPFKELLLAEKWAKMN KLPFPKIDPYVFDREGLKECYVFKPKNPDMEKDCPTIIHFVLANINFRKYRAPGVPRETE EEKEIADFDIFDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRR QNPSRCSVSLSNVEARRFFNKEFLSKPKA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T71B0A | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | ZPL521 | Drug Info | Phase 1/2 | Atopic dermatitis | [1] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | EFIPLADIB | Drug Info | Terminated | Asthma | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 46 Inhibitor drugs | + | ||||
| 1 | ZPL521 | Drug Info | [1] | |||
| 2 | EFIPLADIB | Drug Info | [3] | |||
| 3 | (S)-Ethyl 6-(2-oxohexadecanamido)decanoate | Drug Info | [4] | |||
| 4 | (S)-Methyl 4-(2-oxohexadecanamido)octanoate | Drug Info | [4] | |||
| 5 | (S)-tert-Butyl 4-(2-oxohexadecanamido)pentanoate | Drug Info | [4] | |||
| 6 | (Z)-1,1,1,2,2,3,3-heptafluorohenicos-12-en-4-one | Drug Info | [5] | |||
| 7 | 1,1,1,2,2,3,3,5-octafluoro-8-phenyloctan-4-one | Drug Info | [5] | |||
| 8 | 1,1,1,2,2,3,3-heptafluoro-8-phenyloctan-4-ol | Drug Info | [5] | |||
| 9 | 1,1,1,2,2,4-hexafluoro-7-phenylheptan-3-one | Drug Info | [5] | |||
| 10 | 1,1,1,2,2-Pentafluoro-8-phenyl-octan-3-one | Drug Info | [6] | |||
| 11 | 1,1,1,2,2-Pentafluoro-9-phenyl-nonan-3-one | Drug Info | [6] | |||
| 12 | 1,1,1,3-Tetrafluoro-6-phenylhexan-2-one | Drug Info | [5] | |||
| 13 | 1,1,1,3-Tetrafluoro-7-phenylheptan-2-one | Drug Info | [5] | |||
| 14 | 1,1,1,3-Tetrafluoro-heptadecan-2-one | Drug Info | [6] | |||
| 15 | 1,1,1-Trifluoro-4-(4-hexyloxy-phenyl)-butan-2-one | Drug Info | [6] | |||
| 16 | 1,1,1-Trifluoro-5-(4-octylphenoxy)pentan-2-one | Drug Info | [5] | |||
| 17 | 1,1,1-Trifluoro-6-(4-hexyloxy-phenyl)-hexan-2-one | Drug Info | [6] | |||
| 18 | 1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one | Drug Info | [5] | |||
| 19 | 1,1,1-Trifluoro-7-phenylheptan-2-one | Drug Info | [6] | |||
| 20 | 1,1,1-Trifluoro-8-phenyl-octan-2-one | Drug Info | [6] | |||
| 21 | 1,1,1-trifluoroheptadecan-2-one | Drug Info | [6] | |||
| 22 | 1-Imidazol-1-yl-3-(4-octylphenoxy)propan-2-one | Drug Info | [7] | |||
| 23 | 4-(2-oxohexadecanamido)butanoic acid | Drug Info | [8] | |||
| 24 | 4-(4-Decyloxy-phenyl)-1,1,1-trifluoro-butan-2-one | Drug Info | [6] | |||
| 25 | 6-(4-Decyloxy-phenyl)-1,1,1-trifluoro-hexan-2-one | Drug Info | [6] | |||
| 26 | Allyl 4-(2-oxohexadecanamido)butanoate | Drug Info | [4] | |||
| 27 | AR-C70484XX | Drug Info | [7] | |||
| 28 | ARACHIDONYL TRIFLUOROMETHYLKETONE | Drug Info | [7], [9] | |||
| 29 | AX-006 | Drug Info | [10] | |||
| 30 | AX-048 | Drug Info | [10] | |||
| 31 | ECOPLADIB | Drug Info | [3] | |||
| 32 | Ethyl 2-(2-oxohexadecanamido)acetate | Drug Info | [4] | |||
| 33 | Ethyl 4-(2-oxohexadecanamido)benzoate | Drug Info | [4] | |||
| 34 | Methyl 2-(2-oxo-8-phenyloctanamido)acetate | Drug Info | [4] | |||
| 35 | Methyl 2-(2-oxohexadecanamido)acetate | Drug Info | [4] | |||
| 36 | Methyl arachidonyl fluorophosphonate | Drug Info | [9] | |||
| 37 | N-(4-Ethoxybutyl)-2-oxohexadecanamide | Drug Info | [4] | |||
| 38 | Tert-Butyl 2-(2-oxohexadecanamido)acetate | Drug Info | [4] | |||
| 39 | Tert-Butyl 3-(2-oxo-8-phenyloctanamido)propanoate | Drug Info | [4] | |||
| 40 | Tert-Butyl 3-(2-oxohexadecanamido)propanoate | Drug Info | [4] | |||
| 41 | Tert-Butyl 5-(2-oxohexadecanamido)pentanoate | Drug Info | [4] | |||
| 42 | WAY-196025 | Drug Info | [3] | |||
| 43 | [3,4''']biflavone | Drug Info | [11] | |||
| 44 | [4',4''']-biflavone | Drug Info | [11] | |||
| 45 | [6,3''']biflavone | Drug Info | [11] | |||
| 46 | [6,4''']biflavone | Drug Info | [11] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | Indole 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 3 | Reactions of functionalized sulfonamides: application to lowering the lipophilicity of cytosolic phospholipase A2alpha inhibitors. J Med Chem. 2009 Feb 26;52(4):1156-71. | |||||
| REF 4 | Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A(2) enzymes. Bioorg Med Chem. 2008 Dec 15;16(24):10257-69. | |||||
| REF 5 | Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2. J Med Chem. 2010 May 13;53(9):3602-10. | |||||
| REF 6 | Synthesis of polyfluoro ketones for selective inhibition of human phospholipase A2 enzymes. J Med Chem. 2008 Dec 25;51(24):8027-37. | |||||
| REF 7 | 1-Indol-1-yl-propan-2-ones and related heterocyclic compounds as dual inhibitors of cytosolic phospholipase A(2)alpha and fatty acid amide hydrolase. Bioorg Med Chem. 2010 Jan 15;18(2):945-52. | |||||
| REF 8 | Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha. J Med Chem. 2007 Mar 22;50(6):1380-400. | |||||
| REF 9 | 85-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. | |||||
| REF 10 | 2-Oxoamide inhibitors of phospholipase A2 activity and cellular arachidonate release based on dipeptides and pseudodipeptides. Bioorg Med Chem. 2009 Jul 1;17(13):4833-43. | |||||
| REF 11 | Inhibitory effect of synthetic C-C biflavones on various phospholipase A(2)s activity. Bioorg Med Chem. 2007 Nov 15;15(22):7138-43. | |||||
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