Target Information
| Target General Information | Top | |||||
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| Target ID |
T69912
(Former ID: TTDC00116)
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| Target Name |
Platelet-activating factor acetylhydrolase (PLA2G7)
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| Synonyms |
gVIIA-PLA2; PAFAH; PAF acetylhydrolase; PAF 2-acylhydrolase; Lipoprotein-associated phospholipase A2; LDL-associated phospholipase A2; LDL-PLA(2); Group-VIIA phospholipase A2; 2-acetyl-1-alkylglycerophosphocholine esterase; 1-alkyl-2-acetylglycerophosphocholine esterase
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| Gene Name |
PLA2G7
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Alzheimer disease [ICD-11: 8A20] | |||||
| 2 | Arterial occlusive disease [ICD-11: BD40] | |||||
| 3 | Cardiovascular disease [ICD-11: BA00-BE2Z] | |||||
| Function |
Has a specificity for substrates with a short residue at the sn-2 position. It is inactive against long-chain phospholipids. Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF.
Click to Show/Hide
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| BioChemical Class |
Carboxylic ester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.1.47
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| Sequence |
MVPPKLHVLFCLCGCLAVVYPFDWQYINPVAHMKSSAWVNKIQVLMAAASFGQTKIPRGN
GPYSVGCTDLMFDHTNKGTFLRLYYPSQDNDRLDTLWIPNKEYFWGLSKFLGTHWLMGNI LRLLFGSMTTPANWNSPLRPGEKYPLVVFSHGLGAFRTLYSAIGIDLASHGFIVAAVEHR DRSASATYYFKDQSAAEIGDKSWLYLRTLKQEEETHIRNEQVRQRAKECSQALSLILDID HGKPVKNALDLKFDMEQLKDSIDREKIAVIGHSFGGATVIQTLSEDQRFRCGIALDAWMF PLGDEVYSRIPQPLFFINSEYFQYPANIIKMKKCYSPDKERKMITIRGSVHQNFADFTFA TGKIIGHMLKLKGDIDSNVAIDLSNKASLAFLQKHLGLHKDFDQWDCLIEGDDENLIPGT NINTTNQHIMLQNSSGIEKYN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T37G49 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | GSK2647544 | Drug Info | Phase 1 | Alzheimer disease | [2] | |
| 2 | Rilapladib | Drug Info | Phase 1 | Cardiovascular disease | [3] | |
| Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
| 1 | RPAF-AH | Drug Info | Discontinued in Phase 3 | Sepsis | [4] | |
| 2 | Goxalapladib | Drug Info | Discontinued in Phase 1 | Arteriosclerosis | [5] | |
| 3 | GSK568859 | Drug Info | Discontinued in Phase 1 | Arteriosclerosis | [6] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | GSK2647544 | Drug Info | [7] | |||
| 2 | RPAF-AH | Drug Info | [10] | |||
| 3 | Goxalapladib | Drug Info | [11] | |||
| 4 | GSK568859 | Drug Info | [7] | |||
| Inhibitor | [+] 9 Inhibitor drugs | + | ||||
| 1 | Rilapladib | Drug Info | [1], [8] | |||
| 2 | Bicyclic pyrimidine derivative 2 | Drug Info | [9] | |||
| 3 | Indolizine derivative 1 | Drug Info | [9] | |||
| 4 | (1r)-1,2,2-trimethylpropyl (r)-methylphosphinate | Drug Info | [12] | |||
| 5 | (E)-(thiophen-2-ylmethylidene)amino benzoate | Drug Info | [13] | |||
| 6 | 3,4-difluorobenzaldehyde O-benzoyloxime | Drug Info | [14] | |||
| 7 | 4-fluorobenzaldehyde O-benzoyloxime | Drug Info | [14] | |||
| 8 | Benzaldehyde O-benzoyloxime | Drug Info | [14] | |||
| 9 | SB-381320 | Drug Info | [13] | |||
| 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 Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Ether lipid metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Biosynthesis of antibiotics | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Lissencephaly gene (LIS1) in neuronal migration and development | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | IL1 and megakaryotyces in obesity | |||||
| 2 | Synthesis, Secretion, and Deacylation of Ghrelin | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Phospholipase A2 inhibitors. Curr Opin Lipidol. 2009 Aug;20(4):327-32. | |||||
| REF 2 | ClinicalTrials.gov (NCT01924858) A Positron Emission Tomography (PET) Study to Investigate the Brain Biodistribution of 18F GSK2647544 in Healthy Subjects to Determine Its Ability to Cross the Blood-brain-barrier.. U.S. National Institutes of Health. | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018454) | |||||
| REF 4 | ClinicalTrials.gov (NCT00037687) Safety and Efficacy of Recombinant Human Platelet-Activating Factor Acetylhydrolase for the Treatment of Severe Sepsis. U.S. National Institutes of Health. | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020582) | |||||
| REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025982) | |||||
| REF 7 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1432). | |||||
| REF 8 | THERAPEUTICS: Rilapladib | |||||
| REF 9 | Inhibitors of phospholipase A2 and their therapeutic potential: an update on patents (2012-2016).Expert Opin Ther Pat. 2017 Feb;27(2):217-225. | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006777) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020582) | |||||
| REF 12 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 13 | (E)-Phenyl- and -heteroaryl-substituted O-benzoyl-(or acyl)oximes as lipoprotein-associated phospholipase A2 inhibitors. Bioorg Med Chem Lett. 2005 Mar 1;15(5):1525-7. | |||||
| REF 14 | Potent inhibitors of lipoprotein-associated phospholipase A(2): benzaldehyde O-heterocycle-4-carbonyloxime. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5576-9. | |||||
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