Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDNFMT)

• DTT Name: Platelet-activating factor acetylhydrolase (PLA2G7)
• 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
• Gene Name: PLA2G7
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Alzheimer disease [ICD-11: 8A20]
  Arterial occlusive disease [ICD-11: BD40]
  Cardiovascular disease [ICD-11: BA00-BE2Z]
• BioChemical Class: Carboxylic ester hydrolase
• UniProt ID: PAFA_HUMAN
• TTD ID: T69912
• EC Number: EC 3.1.1.47
• Sequence:
  MVPPKLHVLFCLCGCLAVVYPFDWQYINPVAHMKSSAWVNKIQVLMAAASFGQTKIPRGN
  GPYSVGCTDLMFDHTNKGTFLRLYYPSQDNDRLDTLWIPNKEYFWGLSKFLGTHWLMGNI
  LRLLFGSMTTPANWNSPLRPGEKYPLVVFSHGLGAFRTLYSAIGIDLASHGFIVAAVEHR
  DRSASATYYFKDQSAAEIGDKSWLYLRTLKQEEETHIRNEQVRQRAKECSQALSLILDID
  HGKPVKNALDLKFDMEQLKDSIDREKIAVIGHSFGGATVIQTLSEDQRFRCGIALDAWMF
  PLGDEVYSRIPQPLFFINSEYFQYPANIIKMKKCYSPDKERKMITIRGSVHQNFADFTFA
  TGKIIGHMLKLKGDIDSNVAIDLSNKASLAFLQKHLGLHKDFDQWDCLIEGDDENLIPGT
  NINTTNQHIMLQNSSGIEKYN
• 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.
• KEGG Pathway:
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
• Reactome Pathway: Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK2647544	DM3KARJ	Alzheimer disease	8A20	Phase 1	[2]
Rilapladib	DMB9861	Arteriosclerosis	BD40	Phase 1	[1], [3]

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bicyclic pyrimidine derivative 2	DMJP16K	N. A.	N. A.	Patented	[4]
Indolizine derivative 1	DM4GZBI	N. A.	N. A.	Patented	[4]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RPAF-AH	DMOVJ60	Sepsis	1G40-1G41	Discontinued in Phase 3	[5]
Goxalapladib	DMSGUY9	Arteriosclerosis	BD40	Discontinued in Phase 1	[6]
GSK568859	DM6E84O	Arteriosclerosis	BD40	Discontinued in Phase 1	[2]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(1r)-1,2,2-trimethylpropyl (r)-methylphosphinate	DMVE34H	Discovery agent	N.A.	Investigative	[7]
(E)-(thiophen-2-ylmethylidene)amino benzoate	DMHSJAT	Discovery agent	N.A.	Investigative	[8]
3,4-difluorobenzaldehyde O-benzoyloxime	DMFV3Y9	Discovery agent	N.A.	Investigative	[9]
4-fluorobenzaldehyde O-benzoyloxime	DM2N4BJ	Discovery agent	N.A.	Investigative	[9]
Benzaldehyde O-benzoyloxime	DMB7DFT	Discovery agent	N.A.	Investigative	[9]
SB-381320	DM3BV5S	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Neonatal sepsis	1G41	Whole blood	6.70E-02	-0.48	-0.8
Alzheimer's disease	8A00.0	Entorhinal cortex	5.33E-03	0.09	0.23
Coronary artery disease	BA80-BA8Z	Peripheral blood	2.26E-01	-0.09	-0.29

References

• [1] Phospholipase A2 inhibitors. Curr Opin Lipidol. 2009 Aug;20(4):327-32.
• [2] 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).
• [3] THERAPEUTICS: Rilapladib
• [4] Inhibitors of phospholipase A2 and their therapeutic potential: an update on patents (2012-2016).Expert Opin Ther Pat. 2017 Feb;27(2):217-225.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006777)
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020582)
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [8] (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.
• [9] Potent inhibitors of lipoprotein-associated phospholipase A(2): benzaldehyde O-heterocycle-4-carbonyloxime. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5576-9.