Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTO8QRU)

• DTT Name: Group IIA phospholipase A2 (GIIA sPLA2)
• Synonyms: RASF-A; Phospholipase A2, membrane associated; Phosphatidylcholine 2-acylhydrolase 2A; PLA2L; PLA2B; Non-pancreatic secretory phospholipase A2; NPS-PLA2; GIIC sPLA2
• Gene Name: PLA2G2A
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Carboxylic ester hydrolase
• UniProt ID: PA2GA_HUMAN
• TTD ID: T19160
• EC Number: EC 3.1.1.4
• Sequence:
  MKTLLLLAVIMIFGLLQAHGNLVNFHRMIKLTTGKEAALSYGFYGCHCGVGGRGSPKDAT
  DRCCVTHDCCYKRLEKRGCGTKFLSYKFSNSGSRITCAKQDSCRSQLCECDKAAATCFAR
  NKTTYNKKYQYYSNKHCRGSTPRC
• Function: Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Thought to participate in the regulation of phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Independent of its catalytic activity, acts as a ligand for integrins. Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1. Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1. Induces cell proliferation in an integrin-dependent manner.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Ether lipid metabolism (hsa00565)
  Arachidonic acid metabolism (hsa00590)
  Linoleic acid metabolism (hsa00591)
  alpha-Linolenic acid metabolism (hsa00592)
  Metabolic pathways (hsa01100)
  Ras signaling pathway (hsa04014)
  Vascular smooth muscle contraction (hsa04270)
  Pancreatic secretion (hsa04972)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway:
  Acyl chain remodelling of PE (R-HSA-1482839)
  Acyl chain remodelling of PI (R-HSA-1482922)
  Acyl chain remodelling of PC (R-HSA-1482788)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KH064	DMR1NYF	Breast cancer	2C60-2C65	Clinical trial	[1]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,4-Butanediol	DMVHKZT	Discovery agent	N.A.	Investigative	[2]
2-(4-phenoxyphenoxy)ethanamine	DM7TBUJ	Discovery agent	N.A.	Investigative	[3]
2-Propanol, Isopropanol	DML5O0H	Discovery agent	N.A.	Investigative	[4]
B-Octylglucoside	DMMO75G	Discovery agent	N.A.	Investigative	[5]
BOLINAQUINONE	DMVB6UG	Discovery agent	N.A.	Investigative	[6]
CACOSPONGIONOLIDE	DMIPJUS	Discovery agent	N.A.	Investigative	[7]
CACOSPONGIONOLIDE B	DMCSXNW	Discovery agent	N.A.	Investigative	[7]
Cacospongionolide E	DM2DYAV	Discovery agent	N.A.	Investigative	[7]
DIDODECANOYLPHLOROGLUCINOL	DM2FLRQ	Discovery agent	N.A.	Investigative	[8]
DYSIDINE	DMNYQL9	Discovery agent	N.A.	Investigative	[6]
Elaidoylamide	DMP8VDT	Discovery agent	N.A.	Investigative	[5]
Lauric Acid	DM9C8KQ	Discovery agent	N.A.	Investigative	[5]
LUFFARIELLOLIDE	DMYRCHV	Discovery agent	N.A.	Investigative	[9]
N-Tridecanoic Acid	DMNZ37C	Discovery agent	N.A.	Investigative	[4]
Ochnaflavone	DMGVDR6	Discovery agent	N.A.	Investigative	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Breast cancer	2C82	Breast tissue	6.13E-08	-0.54	-0.33
Rheumatoid arthritis	FA20	Synovial tissue	5.74E-06	2.79	4.17

References

• [1] D-Tyrosine as a chiral precusor to potent inhibitors of human nonpancreatic secretory phospholipase A2 (IIa) with antiinflammatory activity. Chembiochem. 2003 Mar 3;4(2-3):181-5.
• [2] Drosophila metabolize 1,4-butanediol into gamma-hydroxybutyric acid in vivo. Eur J Pharmacol. 2003 Jul 25;473(2-3):149-52.
• [3] Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching. J Med Chem. 2008 Dec 25;51(24):7882-8.
• [4] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A2 and other leukocyte... J Nat Prod. 2001 May;64(5):612-5.
• [7] A new cacospongionolide inhibitor of human secretory phospholipase A2 from the Tyrrhenian sponge Fasciospongia cavernosa and absolute configuration... J Nat Prod. 1998 Jul;61(7):931-5.
• [8] Simplified YM-26734 inhibitors of secreted phospholipase A2 group IIA. Bioorg Med Chem Lett. 2008 Oct 15;18(20):5415-9.
• [9] Phospholipase A2 inhibitors from marine organisms. J Nat Prod. 1992 Dec;55(12):1701-17.
• [10] Synthesis of phospholipase A2 inhibitory biflavonoids. Bioorg Med Chem Lett. 2006 May 1;16(9):2373-5.