PLA2G2A

Summary

PLA2G2A (phospholipase A2 group IIA, HGNC:9031) is a protein-coding gene on chromosome 1p36.13, encoding Phospholipase A2, membrane associated (P14555). Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration.

The protein encoded by this gene is a member of the phospholipase A2 family (PLA2). PLA2s constitute a diverse family of enzymes with respect to sequence, function, localization, and divalent cation requirements. This gene product belongs to group II, which contains secreted form of PLA2, an extracellular enzyme that has a low molecular mass and requires calcium ions for catalysis. It catalyzes the hydrolysis of the sn-2 fatty acid acyl ester bond of phosphoglycerides, releasing free fatty acids and lysophospholipids, and thought to participate in the regulation of the phospholipid metabolism in biomembranes. Several alternatively spliced transcript variants with different 5’ UTRs have been found for this gene.

Source: NCBI Gene 5320 — RefSeq curated summary.

At a glance

• Gene–disease (curated): colorectal cancer (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 33 total — 1 pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001395463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9031
Approved symbol	PLA2G2A
Name	phospholipase A2 group IIA
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188257
Ensembl biotype	protein_coding
OMIM	172411
Entrez	5320

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

ENST00000375111, ENST00000400520, ENST00000461140, ENST00000482011, ENST00000496748, ENST00000649436, ENST00000907283, ENST00000907285, ENST00000907286, ENST00000907287, ENST00000932016, ENST00000962622, ENST00000962623

RefSeq mRNA: 5 — MANE Select: NM_001395463 NM_000300, NM_001161727, NM_001161728, NM_001161729, NM_001395463

CCDS: CCDS201

Canonical transcript exons

ENST00000482011 — 5 exons

Exon	Start	End
ENSE00001878858	19979580	19979618
ENSE00003515687	19978380	19978524
ENSE00003547343	19978015	19978121
ENSE00003674464	19978734	19978879
ENSE00003978109	19975435	19975843

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 99.88.

FANTOM5 (CAGE): breadth broad, TPM avg 35.9484 / max 7355.7046, expressed in 308 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10711	34.9006	303
10709	0.3247	78
10708	0.2408	62
10706	0.1723	51
10705	0.1631	47
10712	0.0644	22
10707	0.0551	19
10710	0.0273	13

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.88	gold quality
pericardium	UBERON:0002407	99.87	gold quality
right coronary artery	UBERON:0001625	99.85	gold quality
ileal mucosa	UBERON:0000331	99.72	gold quality
tendon of biceps brachii	UBERON:0008188	99.72	gold quality
synovial joint	UBERON:0002217	99.68	gold quality
mucosa of stomach	UBERON:0001199	99.67	gold quality
right atrium auricular region	UBERON:0006631	99.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.56	gold quality
left coronary artery	UBERON:0001626	99.53	gold quality
coronary artery	UBERON:0001621	99.50	gold quality
rectum	UBERON:0001052	99.47	gold quality
apex of heart	UBERON:0002098	99.44	gold quality
layer of synovial tissue	UBERON:0007616	99.38	gold quality
cardiac atrium	UBERON:0002081	99.33	gold quality
jejunal mucosa	UBERON:0000399	99.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.00	gold quality
small intestine	UBERON:0002108	98.78	gold quality
duodenum	UBERON:0002114	98.67	gold quality
omental fat pad	UBERON:0010414	98.40	gold quality
mucosa of transverse colon	UBERON:0004991	98.37	gold quality
peritoneum	UBERON:0002358	98.32	gold quality
heart right ventricle	UBERON:0002080	98.28	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.18	gold quality
tibial nerve	UBERON:0001323	97.95	gold quality
popliteal artery	UBERON:0002250	97.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.70	gold quality
tibial artery	UBERON:0007610	97.69	gold quality
lower esophagus	UBERON:0013473	97.65	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	18901.08
E-MTAB-8322	yes	11972.07
E-HCAD-15	yes	5022.42
E-MTAB-8530	yes	1751.05
E-MTAB-10137	yes	897.17
E-GEOD-135922	yes	47.51
E-GEOD-125970	yes	46.32
E-HCAD-1	yes	20.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, CEBPA, CEBPB, CTNNB1, DNMT1, NFATC2, NFKB1, NFKB, PPARA, PPARD, RELA, STAT3, THRB

miRNA regulators (miRDB)

31 targeting PLA2G2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-7847-3P	96.63	64.58	952

Literature-anchored findings (GeneRIF, showing 40)

• data are consistent with the contention that group IIA sPLA2 expression is elevated in neoplastic prostatic tissue and support the hypothesis that dysregulation of sPLA2 may play a role in prostatic carcinogenesis (PMID:11839587)
• Ceramides increase the activity of the secretory phospholipase A2 and alter its fatty acid specificity (PMID:11903045)
• antibacterial properties of PLA2-IIA in human acute phase serum (PMID:12085323)
• determination of binding site preference for membranes with anionic phospholipids (PMID:12244093)
• the potent antistaphylococcal activity of Group IIA PLA(2) depends on cationic properties of the enzyme that promote binding to the cell wall (PMID:12359734)
• The activity of PLA2G2A may suppress progression or metastasis of human gastric cancer. (PMID:12456890)
• The crystal structure of H48Q PLA2 reveals that the active site structure is maintained intact in the mutant and suggests a mechanism in which it is not essential to involve a base (His-48) to deprotonate a water molecule in order to facilitate catalysis. (PMID:12501175)
• Human group IIA PLA2 induces expression of inducible nitric oxide synthase and nitrite production in a dose- and time-dependent manner in activated macrophages of mouse cell line Raw264.7. (PMID:12574380)
• Group IIA secretory PLA2 induces the release of specific granule enzyme beta-glucuronidase, the production of IL-6 and IL-8, and the expression of activation markers (CD44 and CD69) on human eosinophils. (PMID:12626587)
• sPLA2-IIA potentiates the influx of Ca2+ into neurons via L-VSCC; eicosanoids and ROS generated during arachidonic acid oxidative metabolism are involved in sPLA2-IIA-induced apoptosis in cooperation with Ca2+ (PMID:12694401)
• hIIA PLA2 releases arachidonic acid from apoptotic T cells through interactions with heparan sulfate proteoglycans. (PMID:12773489)
• sPLA2-triggered release of fatty acids from erythrocyte membranes is inhibited by phospholipase A2-activating protein (PMID:14499668)
• Stable expression of human groups IIA and X secreted phospholipases A(2) (hGIIA and hGX) in CHO-K1 and HEK293 cells leads to serum- and interleukin-1beta-promoted arachidonate release. (PMID:15007070)
• macrophage sPLA2 IIa is a proatherogenic factor and regulates collagen production in the plaque (PMID:15576846)
• new autocrine and paracrine pathways activating sPLA2-IIA gene expression in rat and human vascular smooth muscle cells (PMID:15802623)
• macrophage-specific overexpression of human sPLA2 increases atherogenesis by directly modulating foam cell formation and in vivo oxidative stress without any effect on systemic sPLA2 activity and lipoprotein metabolism (PMID:15897607)
• sPLA2-IIA expression occurred at higher levels in cystic fibrosis cells than in control cells (PMID:15964894)
• Appreciable bacterial phospholipid degradation occurs only in the presence of catalytically active group IIA-phospholipase A2 and a functional respiratory burst NADPH oxidase in neutrophils. (PMID:16177112)
• Group IIA PLA2 is the major antibacterial factor in human acute phase serum against the gram-positive bacteria Staphylococcus aureus and Listeria monocytogenes, exceeding complement in efficiency (PMID:16253130)
• increased sPLA(2) activity in inflammation in the presence of cells that have lost their membrane phospholipid asymmetry can lead to LPA-mediated endothelial dysfunction and loss of vascular integrity (PMID:16278219)
• PLA2G2A haplotypic variation strongly impacts on phospholipase A(2)IIa levels which are related to higher risk of coronary artery disease in patients with Type II diabetes mellitus. (PMID:16368710)
• A mechanism is indicated for phospholipase A2 type IIa (PLA2-IIA) to target perturbed native membranes with low global anionic lipid contents. (PMID:16461407)
• This study reviews the evidence and discusses the potential roles of phospholipase A2 Group 2A for schizophrenia with particular emphasis on published association studies. (PMID:16585943)
• cytosolic and group IIA secreted phospholipases A(2) work together to liberate arachidonate from phospholipids in response to cytokines (PMID:16603549)
• cPLA2beta3 is a novel variant localized to mitochondria and early endosomes (PMID:16617059)
• large differences in activities result from distinct conformational changes in PLA(2)s upon membrane binding (PMID:17029400)
• Phospholipase A2 Group IIa may be a modifier gene for fundic gland polyposis in patients with familial adenomatous polyposis (PMID:17164967)
• Analysis of the lipid extracts of supernatants and cell pellets as well as pharmacological studies with calpeptin and the cytosolic phospholipase A2 (PLA2) inhibitor pyrrolidine-1 showed the dependence of AA release on cytosolic PLA2-catalyzed reactions. (PMID:17264305)
• Mean platelet PLA(2) activity was increased in individuals with Alzheimer’s disease,vascular dementia and stroke. (PMID:17447002)
• sPLA2-IIA tSNP haplotypes do not show association with total and LDL cholesterol and oxLDL/LDL (PMID:17545304)
• Intercellular PLA2 expression and location in human macrophages: influence of synthetic material surface chemistry are reported. (PMID:17565722)
• This enzyme may be a useful guide for therapeutic efficacy and cardiovascular risk assessment. [REVIEW] (PMID:17892360)
• sPLA2-IIa activity may serve a dual role in breast carcinogenesis, beneficial in its release of arachidonate and detrimental in the metabolic conversion of arachadonic acid into prostaglandins and leukotrienes. (PMID:17932742)
• Activatted protein C(APC) effectively suppresses up-regulated sPLA(2)-IIA expressionwhich might contribute to the reported beneficial effects of APC in the treatment of severe inflammatory disorders. (PMID:17936881)
• increased flux of cholesterol from HDL into the liver via SR-BI as a result of PLA2G2A modification of the HDL particle translates neither into increased biliary and fecal sterol output nor into increased gallstone formation (PMID:18037706)
• The enzyme produced supramolecular aggregates with anionic phospholipid vesicles as a result of bridging between particles, a property that is unique to this globally cationic IIA PLA2. (PMID:18089561)
• These data demonstrated that interactions with sPLA(2) observed in artificial bilayers apply to biological membranes. (PMID:18192373)
• Current knowledge about the various links of sPLA2-IIA to cancer of the gastro-intestinal tract, and several models to illustrate its putative biological effects on tumor development.[REVIEW] (PMID:18508504)
• results highlight the complexity of PLA2G2A regulation and provide functional evidence for PLA2G2A as an important regulator of invasion and metastasis in gastric cancer (PMID:18519687)
• Human cardiac myxoma exhibits highly positive phospholipase A2, group IIA, immunophenotype (100% positive cases). (PMID:18540439)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pla2g2a	ENSMUSG00000058908
rattus_norvegicus	Pla2g2a	ENSRNOG00000016945
caenorhabditis_elegans		WBGENE00007419
caenorhabditis_elegans		WBGENE00015406

Paralogs (8): PLA2G10 (ENSG00000069764), PLA2G2D (ENSG00000117215), PLA2G5 (ENSG00000127472), PLA2G2F (ENSG00000158786), PLA2G1B (ENSG00000170890), PLA2G2C (ENSG00000187980), PLA2G2E (ENSG00000188784), OC90 (ENSG00000253117)

Protein

Protein identifiers

Phospholipase A2, membrane associated — P14555 (reviewed: P14555)

Alternative names: GIIC sPLA2, Group IIA phospholipase A2, Non-pancreatic secretory phospholipase A2, Phosphatidylcholine 2-acylhydrolase 2A

All UniProt accessions (2): A0A3B3IRX2, P14555

UniProt curated annotations — full annotation on UniProt →

Function. Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines. Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response. Plays a stem cell regulator role in the intestinal crypt. Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration. May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines. 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.

Subcellular location. Secreted. Cell membrane. Mitochondrion outer membrane.

Tissue specificity. Expressed in various tissues including heart, kidney, liver, lung, pancreas, placenta, skeletal muscle, prostate, ovary, colon and small intestine. Not detected in lymphoid organs and brain. Expressed in platelets (at protein level).

Cofactor. Binds 1 Ca(2+) ion per subunit.

Miscellaneous. Group II phospholipase A2 is found in many cells and also extracellularly. The membrane-bound and secreted forms are identical and are encoded by a single gene. Interaction with integrin ITGA4:ITGB3 is inhibited by a number of synthetic peptides including R-Ala-Trp-Asp-Ile and R-Gly-Arg-Gly-Asp-Asp-Asp which bind to PLA2G2A and disrupt its integrin-binding activity.

Similarity. Belongs to the phospholipase A2 family.

RefSeq proteins (5): NP_000291, NP_001155199, NP_001155200, NP_001155201, NP_001382392* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001211	PLA2	Family
IPR016090	PLA2-like_dom	Domain
IPR033112	PLA2_Asp_AS	Active_site
IPR033113	PLA2_histidine	Active_site
IPR036444	PLipase_A2_dom_sf	Homologous_superfamily

Pfam: PF00068

Enzyme classification (BRENDA):

• EC 3.1.1.4 — phospholipase A2 (BRENDA: 129 organisms, 452 substrates, 710 inhibitors, 90 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

58 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PHOSPHATIDYLCHOLINE	0.05–17	12
1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.94–13.85	7
PHOSPHATIDYLETHANOLAMINE	0.02–10.5	5
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOPHORYLCHOLINE	1.12–5.13	3
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	3–3.92	3
1,2-DIOCTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.12–3.2	3
1-HEXADECYL-2-ACETYL-SN-GLYCEROL-3-PHOSPHOCHOLIN	0.0137–0.0142	2
1-PALMITOYL-2-ARACHIDONYLPHOSPHATIDYLCHOLINE	0.0016–0.0033	2
LECITHIN	8.3–8.5	2
(3E)-3-[(3AS,7AS)-3-METHYL-2-OXO-6-(PROPAN-2-YLI	0.742	1
(3R,3AS,5AS,8BR)-3,5A,5B-TRIMETHYL-3A,4,5,5A,5B,	0.746	1
(3R,3AS,5AS,9BR)-3,5A,9-TRIMETHYL-3A,4,5,5A-TETR	0.734	1
(3R,3AS,6R,8S,9BS)-6,8-DIHYDROXY-3,6,9-TRIMETHYL	0.744	1
(3R,3AS,6R,8S,9BS)-8-HYDROXY-3,6,9-TRIMETHYL-2-O	0.738	1
(3R,3AS,6R,9BS)-3,6,9-TRIMETHYL-2,8-DIOXO-2,3,3A	0.742	1

Catalyzed reactions (Rhea), 12 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:15801)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+) (RHEA:38779)
• 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:40431)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:40811)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z,12Z)-octadecadienoate + H(+) (RHEA:40815)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+) (RHEA:40911)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1’-sn-glycerol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) + (9Z)-octadecenoate + H(+) (RHEA:40919)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:41223)
• 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) (RHEA:41231)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoglycerol + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoglycerol + (9Z)-octadecenoate + H(+) (RHEA:44524)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + H2O = a 1-acyl-sn-glycero-3-phosphoethanolamine + a fatty acid + H(+) (RHEA:44604)
• N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-hexadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+) (RHEA:45424)

UniProt features (55 total): mutagenesis site 22, helix 8, disulfide bond 7, binding site 4, strand 4, active site 2, turn 2, site 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
3U8I	X-RAY DIFFRACTION	1.1
1N28	X-RAY DIFFRACTION	1.5
5G3N	X-RAY DIFFRACTION	1.8
3U8D	X-RAY DIFFRACTION	1.8
1KVO	X-RAY DIFFRACTION	2
1KQU	X-RAY DIFFRACTION	2.1
1POD	X-RAY DIFFRACTION	2.1
1POE	X-RAY DIFFRACTION	2.1
1BBC	X-RAY DIFFRACTION	2.2
1DB4	X-RAY DIFFRACTION	2.2
1J1A	X-RAY DIFFRACTION	2.2
3U8B	X-RAY DIFFRACTION	2.3
3U8H	X-RAY DIFFRACTION	2.3
1AYP	X-RAY DIFFRACTION	2.57
1N29	X-RAY DIFFRACTION	2.6
1DCY	X-RAY DIFFRACTION	2.7
1DB5	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14555-F1	91.22	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 67; 111; 94 (important for integrin binding); 120 (important for integrin binding)

Ligand- & substrate-binding residues (4): 47; 49; 51; 68

Disulfide bonds (7): 46–137, 48–64, 63–117, 69–144, 70–110, 79–103, 97–108

Mutagenesis-validated functional residues (22):

Position	Phenotype
27	reduces bactericidal activity to 20% against b.subtilis and to 4% against s.aureus. complete loss of bactericidal activi
30	complete loss of bactericidal activity; when associated with e-27 and e-35.
35	complete loss of bactericidal activity; when associated with e-27 and e-30.
49	no effect on integrin binding; when associated with k-68.
57	impairs bactericidal activity; when associated with e-128.
62	no effect on integrin binding.
67	catalytically inactive but does not affect integrin binding. impairs leukotriene b4 synthesis in activated neutrophils.
68	no effect on integrin binding; when associated with s-49.
72	impairs bactericidal activity; when associated with e-73 and e-77.
73	impairs bactericidal activity; when associated with e-72 and e-77.
73	slightly reduced integrin binding.
77	impairs bactericidal activity; when associated with e-72 and e-73.
87	reduces bactericidal activity to 20% against b.subtilis and to 10% against s.aureus. complete loss of bactericidal activ
94	moderately reduced integrin binding. greatly reduced integrin binding but no effect on catalytic activity; when associat
99	reduces bactericidal activity to 25% against b.subtilis and to 10% against s.aureus. complete loss of bactericidal activ
104	reduces bactericidal activity to 18% against b.subtilis and to 12% against s.aureus. complete loss of bactericidal activ
120	moderately reduced integrin binding. greatly reduced integrin binding but no effect on catalytic activity; when associat
122	impairs bactericidal activity; when associated with e-127.
127	impairs bactericidal activity; when associated with e-122.
128	impairs bactericidal activity; when associated with e-57.
135	impairs bactericidal activity; when associated with d-138.
138	impairs bactericidal activity; when associated with e-135.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1482788	Acyl chain remodelling of PC
R-HSA-1482801	Acyl chain remodelling of PS
R-HSA-1482839	Acyl chain remodelling of PE
R-HSA-1482922	Acyl chain remodelling of PI
R-HSA-1482925	Acyl chain remodelling of PG
R-HSA-1483166	Synthesis of PA
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 286 (showing top): MODULE_172, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, KEGG_MAPK_SIGNALING_PATHWAY, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_RESPONSE_TO_ANGIOTENSIN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION

GO Biological Process (20): phospholipid metabolic process (GO:0006644), inflammatory response (GO:0006954), positive regulation of macrophage derived foam cell differentiation (GO:0010744), lipid catabolic process (GO:0016042), killing of cells of another organism (GO:0031640), low-density lipoprotein particle remodeling (GO:0034374), intestinal stem cell homeostasis (GO:0036335), angiotensin-activated signaling pathway (GO:0038166), negative regulation of T cell proliferation (GO:0042130), phosphatidylethanolamine metabolic process (GO:0046337), phosphatidylcholine metabolic process (GO:0046470), phosphatidylglycerol metabolic process (GO:0046471), phosphatidic acid metabolic process (GO:0046473), arachidonate secretion (GO:0050482), positive regulation of inflammatory response (GO:0050729), defense response to Gram-positive bacterium (GO:0050830), positive regulation of ERK1 and ERK2 cascade (GO:0070374), regulation of neutrophil activation (GO:1902563), lipid metabolic process (GO:0006629), defense response to bacterium (GO:0042742)

GO Molecular Function (7): A2-type glycerophospholipase activity (GO:0004623), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), obsolete calcium-dependent phospholipase A2 activity (GO:0047498), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (11): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), secretory granule (GO:0030141), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), mitochondrion (GO:0005739), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	6
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycerophospholipid metabolic process	4
cellular anatomical structure	3
cytoplasm	3
lipid metabolic process	2
defense response	2
endomembrane system	2
intracellular membrane-bounded organelle	2
organophosphate metabolic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
catabolic process	1
cell killing	1
disruption of cell in another organism	1
plasma lipoprotein particle remodeling	1
homeostasis of number of cells	1
G protein-coupled receptor signaling pathway	1
cellular response to angiotensin	1
T cell proliferation	1
regulation of T cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
icosanoid secretion	1
arachidonate transport	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
defense response to bacterium	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
regulation of leukocyte activation	1
neutrophil activation	1
primary metabolic process	1
response to bacterium	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
metal ion binding	1
lipid binding	1

Protein interactions and networks

STRING

1574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLA2G2A	PLA2R1	Q13018	930
PLA2G2A	PLA2G4A	P47712	918
PLA2G2A	PLA2G12A	Q9BZM1	875
PLA2G2A	PLA2G3	Q9NZ20	874
PLA2G2A	PLA2G6	O60733	823
PLA2G2A	PLA2G12B	Q9BX93	793
PLA2G2A	PTGS2	P35354	792
PLA2G2A	LTA4H	P09960	745
PLA2G2A	PLA2G7	Q13093	712
PLA2G2A	CALML5	Q9NZT1	669
PLA2G2A	CALML4	Q96GE6	669
PLA2G2A	CALML3	P27482	668
PLA2G2A	CALM1	P02593	666
PLA2G2A	CALML6	Q8TD86	665
PLA2G2A	ENPP2	Q13822	645

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ALOX12	PLA2G2A	psi-mi:“MI:0915”(physical association)	0.400
CRELD2	PLA2G2A	psi-mi:“MI:0915”(physical association)	0.370
CEP70	PLA2G2A	psi-mi:“MI:0915”(physical association)	0.370
PLA2G2A	CRMP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): VIM (Affinity Capture-MS), VIM (Affinity Capture-Western), VIM (Reconstituted Complex), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity), PLA2G2A (Biochemical Activity)

ESM2 similar proteins: A8CG90, F8QN51, F8QN53, O42187, P00592, P00593, P00594, P04054, P04055, P04056, P04416, P04417, P06596, P0DJN7, P11407, P14419, P14421, P14423, P14424, P14555, P20255, P20256, P20258, P20259, P24293, P34180, P43434, P59170, P59172, P81236, P81237, Q1ZY03, Q2YHJ2, Q2YHJ7, Q6EER3, Q6EER4, Q6EER5, Q6EER6, Q71QE8, Q7M334

Diamond homologs: A0A411EZW9, A8CG78, A8CG84, A8CG86, A8CG87, A8E2V8, B5U6Z2, B6CQR5, C0HJC1, C0HKC3, C0HKC4, C0HLF0, C0HLL2, C0HMB2, C3W4R6, C9DPL5, F8QN51, F8QN52, F8QN53, F8QN54, G3DT18, O42187, O42188, O42189, O42190, P00626, P04417, P06860, P08878, P0CAR9, P0DJP4, P0DKR3, P0DKR5, P0DKU1, P0DPS4, P11407, P14420, P14423, P14424, P14555

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

33 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	23
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
13635	NM_001395463.1(PLA2G2A):c.144_145del (p.Cys48fs)	Pathogenic

SpliceAI

638 predictions. Top by Δscore:

Variant	Effect	Δscore
1:19975852:A:C	acceptor_gain	1.0000
1:19978378:A:AC	donor_gain	1.0000
1:19978379:C:CC	donor_gain	1.0000
1:19978379:CCGAT:C	donor_gain	1.0000
1:19978392:T:TA	donor_gain	1.0000
1:19975841:TTG:T	acceptor_gain	0.9900
1:19975844:C:CC	acceptor_gain	0.9900
1:19975851:C:CT	acceptor_gain	0.9900
1:19975852:A:AC	acceptor_gain	0.9900
1:19978014:CCA:C	donor_gain	0.9900
1:19978373:GCCTC:G	donor_loss	0.9900
1:19978374:CCTCA:C	donor_loss	0.9900
1:19978375:CTCA:C	donor_loss	0.9900
1:19978376:TCA:T	donor_loss	0.9900
1:19978377:CACC:C	donor_loss	0.9900
1:19978378:ACC:A	donor_loss	0.9900
1:19978520:TAGGC:T	acceptor_gain	0.9900
1:19978522:GGC:G	acceptor_gain	0.9900
1:19978523:GCCT:G	acceptor_loss	0.9900
1:19978525:C:CC	acceptor_gain	0.9900
1:19978525:CT:C	acceptor_loss	0.9900
1:19978526:T:G	acceptor_loss	0.9900
1:19975839:TTTTG:T	acceptor_gain	0.9800
1:19975840:TTTG:T	acceptor_gain	0.9800
1:19975842:TG:T	acceptor_gain	0.9800
1:19975844:C:T	acceptor_loss	0.9800
1:19975852:A:T	acceptor_gain	0.9800
1:19978008:CTCTT:C	donor_loss	0.9800
1:19978009:TCTTA:T	donor_loss	0.9800
1:19978010:CTTAC:C	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002452 (1:19980526 C>T), RS1000136426 (1:19980338 C>T), RS1000705343 (1:19979666 G>A), RS1001223805 (1:19979411 A>T), RS1001344408 (1:19975205 G>A,C), RS1001507975 (1:19980766 T>A), RS1001555104 (1:19979927 A>AG), RS1001879676 (1:19979929 G>A,C,T), RS1002108175 (1:19980138 G>T), RS1002643575 (1:19981674 G>A,T), RS1002726824 (1:19977084 C>T), RS1002917769 (1:19981841 C>A,T), RS1003001361 (1:19977409 G>A), RS1003593354 (1:19975934 T>C), RS1003812710 (1:19977066 C>T)

Disease associations

OMIM: gene MIM:172411 | disease phenotypes: MIM:246450

GenCC curated gene-disease

Disease	Classification	Inheritance
colorectal cancer	Limited	Autosomal dominant

Mondo (3): familial colorectal cancer (MONDO:0023113), 3-hydroxy-3-methylglutaric aciduria (MONDO:0009520), colorectal cancer (MONDO:0005575)

Orphanet (1): 3-hydroxy-3-methylglutaric aciduria (Orphanet:20)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002891	Uterine leiomyosarcoma
HP:0003003	Colon cancer
HP:0005584	Renal cell carcinoma
HP:0006716	Hereditary nonpolyposis colorectal carcinoma
HP:0006740	Transitional cell carcinoma of the bladder
HP:0006753	Neoplasm of the stomach

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004028_1	Immunoglobulin light chain (AL) amyloidosis	1.000000e-06
GCST006585_38	Blood protein levels	2.000000e-111
GCST008260_1	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	0.000000e+00
GCST008260_12	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	2.000000e-11
GCST008260_2	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	0.000000e+00
GCST008260_3	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	4.000000e-138
GCST008260_4	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	6.000000e-79
GCST008260_7	Group IIA secretory phospholipase A2 levels in individuals with elevated hsCRP	2.000000e-31

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538324	3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3474 (SINGLE PROTEIN), CHEMBL4524005 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 279,374 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL384467	DEXAMETHASONE	4	279,102
CHEMBL148674	VARESPLADIB	2	272

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
varespladib	Inhibition	8.05	pIC50
KH064	Inhibition	7.5	pIC50
compound 12e [PMID: 18605714]	Inhibition	7.4	pIC50
manoalide	Inhibition	5.41	pIC50

Binding affinities (BindingDB)

25 measured of 32 human assays (53 total across all organisms); most potent 25 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(6R)-11-[[4-[[2-[cyclopropyl(difluoro)methyl]-4-pyridinyl]oxy]-3,5-difluorophenyl]methoxy]-2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-dien-9-one	IC50	0.12 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(4S,6R,7S)-12-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]-2,9,11-triazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),11-dien-10-one	IC50	0.141 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(6R)-11-[[4-[(2-cyclopropyl-4-pyridinyl)oxy]-3,5-difluorophenyl]methoxy]-2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-dien-9-one	IC50	0.191 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(6R)-11-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]spiro[2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-diene-3,1’-cyclopropane]-9-one	IC50	0.191 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(4R,6S,7R)-12-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]-2,9,11-triazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),11-dien-10-one	IC50	0.209 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
12-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]-2,9,11-triazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),11-dien-10-one	IC50	0.219 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(6R)-11-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]spiro[2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-diene-4,1’-cyclopropane]-9-one	IC50	0.282 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
11-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]spiro[2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-diene-4,1’-cyclobutane]-9-one	IC50	0.288 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(6R)-11-[[4-[[2-[cyclobutyl(difluoro)methyl]-4-pyridinyl]oxy]-3,5-difluorophenyl]methoxy]-2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-dien-9-one	IC50	0.427 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(1R,10R,11S)-5-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]-2,6,8-triazatetracyclo[9.2.1.02,10.03,8]tetradeca-3,5-dien-7-one	IC50	0.525 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(6R)-11-[[4-[[2-[(3,3-difluorocyclobutyl)-difluoromethyl]-4-pyridinyl]oxy]-3,5-difluorophenyl]methoxy]-2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-dien-9-one	IC50	0.603 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(1S,10R,11S)-5-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]-2,6,8-triazatetracyclo[9.2.1.02,10.03,8]tetradeca-3,5-dien-7-one	IC50	0.617 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(6S)-11-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]spiro[2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-diene-4,1’-cyclopropane]-9-one	IC50	1.07 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
(6S)-11-[[3,5-difluoro-4-[[2-(trifluoromethyl)-4-pyridinyl]oxy]phenyl]methoxy]spiro[2,8,10-triazatricyclo[6.4.0.02,6]dodeca-1(12),10-diene-4,1’-cyclobutane]-9-one	IC50	1.91 nM	US-20250154153: DIHYDROIMIDAZO-PYRIMIDINONE COMPOUNDS AS LP-PLA2 INHIBITORS AND USE THEREOF
2-{1-[(2-{[5-(2-{[3-(carbamoylmethyl)-5-methoxy-2-methyl-1H-indol-1-yl]methyl}phenoxy)pentyl]oxy}phenyl)methyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetamide	IC50	24 nM
2-{1-[(2-{[6-(2-{[3-(carbamoylmethyl)-5-methoxy-2-methyl-1H-indol-1-yl]methyl}phenoxy)hexyl]oxy}phenyl)methyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetamide	IC50	39 nM
2-[1-({2-[3-(2-{[3-(carbamoylmethyl)-5-methoxy-2-methyl-1H-indol-1-yl]methyl}phenoxy)propoxy]phenyl}methyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide	IC50	48 nM
Bis-indole Derivative, 9	IC50	49 nM
2-{1-[(2-{[7-(2-{[3-(carbamoylmethyl)-5-methoxy-2-methyl-1H-indol-1-yl]methyl}phenoxy)heptyl]oxy}phenyl)methyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetamide	IC50	52 nM
2-{1-[(2-{[8-(2-{[3-(carbamoylmethyl)-5-methoxy-2-methyl-1H-indol-1-yl]methyl}phenoxy)octyl]oxy}phenyl)methyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetamide	IC50	58 nM
2-[1-({2-[4-(2-{[3-(carbamoylmethyl)-5-methoxy-2-methyl-1H-indol-1-yl]methyl}phenoxy)butoxy]phenyl}methyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide	IC50	60 nM
Bis-indole Derivative, 10	IC50	76 nM
Bis-indole Derivative, 11	IC50	86 nM
2-(5-methoxy-2-methyl-1-{[2-(pentyloxy)phenyl]methyl}-1H-indol-3-yl)acetamide	IC50	120 nM
2-(1-benzyl-5-methoxy-2-methyl-1H-indol-3-yl)acetamide	EC50	1500 nM

ChEMBL bioactivities

473 potent at pChembl≥5 of 576 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.85	IC50	1.4	nM	CHEMBL5172164
8.52	IC50	3	nM	CHEMBL180576
8.52	IC50	3	nM	CHEMBL332993
8.52	IC50	3	nM	CHEMBL357979
8.40	IC50	4	nM	CHEMBL425696
8.40	IC50	4	nM	CHEMBL436456
8.30	IC50	5	nM	CHEMBL5208632
8.22	IC50	6	nM	CHEMBL361552
8.22	IC50	6	nM	CHEMBL357979
8.22	IC50	6	nM	CHEMBL332993
8.22	IC50	6	nM	CHEMBL359005
8.22	IC50	6	nM	CHEMBL356606
8.22	IC50	6	nM	CHEMBL347957
8.22	IC50	6	nM	CHEMBL345488
8.15	IC50	7	nM	VARESPLADIB
8.15	IC50	7	nM	CHEMBL179658
8.15	IC50	7	nM	CHEMBL180576
8.15	IC50	7	nM	CHEMBL5177527
8.15	IC50	7	nM	CHEMBL345986
8.10	IC50	8	nM	CHEMBL5172164
8.10	IC50	8	nM	CHEMBL433701
8.10	IC50	8	nM	CHEMBL355944
8.10	IC50	8	nM	CHEMBL347748
8.05	IC50	9	nM	CHEMBL179118
8.05	IC50	9	nM	CHEMBL355944
8.05	IC50	9	nM	VARESPLADIB
8.05	IC50	9	nM	CHEMBL357804
8.05	IC50	9	nM	CHEMBL422667
8.05	IC50	9	nM	CHEMBL148795
8.00	IC50	10	nM	CHEMBL179966
8.00	IC50	10	nM	CHEMBL361552
8.00	IC50	10	nM	CHEMBL425869
8.00	IC50	10	nM	CHEMBL4593409
8.00	IC50	10	nM	CHEMBL423762
8.00	IC50	10	nM	CHEMBL5172164
8.00	IC50	10	nM	CHEMBL422667
7.96	IC50	11	nM	CHEMBL435488
7.96	IC50	11	nM	CHEMBL425696
7.96	IC50	11	nM	CHEMBL4451830
7.96	IC50	11	nM	CHEMBL346196
7.96	IC50	11	nM	CHEMBL359005
7.96	IC50	11	nM	CHEMBL148649
7.92	IC50	12	nM	VARESPLADIB
7.92	IC50	12	nM	CHEMBL4457557
7.89	IC50	13	nM	VARESPLADIB
7.89	IC50	13	nM	CHEMBL179658
7.89	IC50	13	nM	CHEMBL148649
7.85	IC50	14	nM	CHEMBL423762
7.85	IC50	14	nM	CHEMBL514841
7.82	IC50	15	nM	CHEMBL359304

PubChem BioAssay actives

496 with measured affinity, of 1120 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[2-methyl-1-oxamoyl-3-[(2-phenylphenyl)methyl]indolizin-8-yl]oxyacetic acid	1894718: Inhibition of human group IIA phospholipase A2 preincubated with compound for 10 mins followed by enzyme addition and measured after 30 mins by PC/DOC assay	ic50	0.0014	uM
2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-methyl-6,7,8,9-tetrahydrobenzo[g]indol-3-yl]-2-oxoacetamide	242401: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0030	uM
2-[2-methyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]indol-4-yl]oxyacetic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0030	uM
2-[2-ethyl-1-oxamoyl-3-[(2-phenylphenyl)methyl]indolizin-8-yl]oxyacetic acid	1894718: Inhibition of human group IIA phospholipase A2 preincubated with compound for 10 mins followed by enzyme addition and measured after 30 mins by PC/DOC assay	ic50	0.0030	uM
2-[1-(cyclohexylmethyl)-2-methyl-3-oxamoylbenzo[g]indol-4-yl]oxyacetic acid	242401: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0040	uM
2-[1-[(2-benzylphenyl)methyl]-2-ethyl-3-oxamoylindol-4-yl]oxyacetic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0040	uM
2-[1-(2-amino-2-oxoethyl)-2-ethyl-3-(naphthalen-1-ylmethyl)indolizin-8-yl]oxyacetic acid	1894718: Inhibition of human group IIA phospholipase A2 preincubated with compound for 10 mins followed by enzyme addition and measured after 30 mins by PC/DOC assay	ic50	0.0050	uM
2-[(1-benzyl-2-methyl-3-oxamoyl-7,8-dihydro-6H-cyclopenta[g]indol-4-yl)oxy]acetic acid	242401: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0060	uM
(2R)-2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxypropanoic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0060	uM
2-[2-cyclopropyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]indol-4-yl]oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0060	uM
2-[1-[(2,6-dichlorophenyl)methyl]-2-methyl-3-oxamoylindol-4-yl]oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0060	uM
2-[2-ethyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]indol-4-yl]oxyacetic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0060	uM
2-[(1-benzyl-2-ethyl-3-oxamoyl-7,8-dihydro-6H-cyclopenta[g]indol-4-yl)oxy]acetic acid	242401: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0070	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxyacetic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0070	uM
2-[2-methyl-3-[(2-phenylphenyl)methyl]-8-(tetrazol-1-ylmethoxy)indolizin-1-yl]-2-oxoacetamide	1894717: Inhibition of human group IIA phospholipase A2 incubated for 30 mins by automatic plate reader analysis	ic50	0.0070	uM
2-[1-[(3-chlorophenyl)methyl]-2-ethyl-3-oxamoylindol-4-yl]oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0070	uM
2-(2-methyl-1-octyl-3-oxamoylindol-4-yl)oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0080	uM
2-(1-benzyl-2-ethyl-6-methyl-3-oxamoylindol-4-yl)acetic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0080	uM
2-[2-methyl-3-oxamoyl-1-[(3-phenylphenyl)methyl]indol-4-yl]oxyacetic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0080	uM
2-[[1-[(2-fluorophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6H-cyclopenta[g]indol-4-yl]oxy]acetic acid	242469: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0090	uM
2-[1-[(2-chlorophenyl)methyl]-2-methyl-3-oxamoylindol-4-yl]oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0090	uM
2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxypropanoic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0090	uM
2-[2-methyl-1-(naphthalen-1-ylmethyl)-3-oxamoylindol-4-yl]oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0090	uM
2-[(1-benzyl-2-methyl-3-oxamoyl-6,7,8,9-tetrahydrobenzo[g]indol-4-yl)oxy]acetic acid	242469: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0100	uM
2-[[1-[(3-fluorophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6H-cyclopenta[g]indol-4-yl]oxy]acetic acid	242469: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0100	uM
(2R)-3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]-2-methylpropanoic acid	1631095: Inhibition of recombinant sPLA2-2A (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by colorimetric method	ic50	0.0100	uM
sodium 2-[3-(2-amino-2-oxoethyl)-2-methyl-1-[(2-phenylphenyl)methyl]indol-4-yl]oxyacetate	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0100	uM
2-[(1-benzyl-2-ethyl-3-oxamoyl-6,7,8,9-tetrahydrobenzo[g]indol-4-yl)oxy]acetic acid	242469: Inhibitory concentration against human nonpancreatic secretory phospholipase A2	ic50	0.0110	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxypropanoic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0110	uM
3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]-2-methylpropanoic acid	1631095: Inhibition of recombinant sPLA2-2A (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by colorimetric method	ic50	0.0110	uM
2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0110	uM
3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]propanoic acid	1631095: Inhibition of recombinant sPLA2-2A (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by colorimetric method	ic50	0.0120	uM
2-(1-benzyl-2-ethyl-4-methoxybenzo[g]indol-3-yl)-2-oxoacetamide	341241: Inhibition of human group2A phospholipase A2 fluorimetric assay	ic50	0.0140	uM
2-[2-methyl-1-[(2-methylphenyl)methyl]-3-oxamoylindol-4-yl]oxyacetic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0150	uM
3-[3-(2-amino-2-oxoethyl)-1-benzyl-2-ethyl-6-methylindol-5-yl]oxypropylphosphonic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0150	uM
3-[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethylindol-5-yl]oxypropylphosphonic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0160	uM
3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]-2-cyclopropylpropanoic acid	1631095: Inhibition of recombinant sPLA2-2A (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by colorimetric method	ic50	0.0180	uM
4-[3-(2-amino-2-oxoethyl)-1-benzyl-2-bromo-6-chloroindol-5-yl]oxybutanoic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0200	uM
sodium 2-[3-(2-amino-2-oxoethyl)-1-[(3-chlorophenyl)methyl]-2-methylindol-4-yl]oxyacetate	159096: Inhibitory activity against porcine pancreatic Phospholipase A2	ic50	0.0200	uM
(4S)-5-(4-benzylphenyl)sulfanyl-4-(7-phenylheptanoylamino)pentanoic acid	158933: Compound was tested for in vitro activity against S-phospholipase A2 (s-PLA2) isolated from human platelets	ic50	0.0210	uM
2-[[3-(5-benzyl-2-carbamoylphenyl)phenyl]methyl]butanoic acid	1631095: Inhibition of recombinant sPLA2-2A (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by colorimetric method	ic50	0.0210	uM
4-[3-(2-amino-2-oxoethyl)-1-benzyl-2-ethyl-6-methylindol-5-yl]sulfanylbutanoic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0220	uM
3-[3-(2-amino-2-oxoethyl)-2-methyl-1-[(2-phenylphenyl)methyl]indol-5-yl]oxypropylphosphonic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0220	uM
4-[3-(2-amino-2-oxoethyl)-1-benzyl-2-ethylindol-5-yl]sulfanylbutanoic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0230	uM
3-[3-(2-amino-2-oxoethyl)-1-benzyl-2-ethylindol-5-yl]oxypropylphosphonic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0230	uM
2-[3-(2-amino-2-oxoethyl)-1-benzyl-2-ethylindol-4-yl]oxyacetic acid	158934: Inhibition of human non-pancreatic secretory phospholipase A2 (PLA2) in a chromogenic assay	ic50	0.0240	uM
2-[1-[[2-[5-[2-[[3-(2-amino-2-oxoethyl)-5-methoxy-2-methylindol-1-yl]methyl]phenoxy]pentoxy]phenyl]methyl]-5-methoxy-2-methylindol-3-yl]acetamide	1798357: Enzymatic Inhibition Assay from Article 10.1021/jm7010707: “Chemically induced dimerization of human nonpancreatic secretory phospholipase A2 by bis-indole derivatives.”	ic50	0.0240	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxy-2-methylpropanoic acid	158931: Inhibition of human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0250	uM
2-(1-benzyl-2-ethyl-3-oxamoylindol-4-yl)oxy-4-phenylbutanoic acid	158930: Inhibition of human nonpancreatic secretory Phospholipase A2 through DOC/PC assay	ic50	0.0260	uM
2-[1-(benzenesulfonyl)-2-ethyl-3-oxamoylindol-4-yl]acetic acid	158932: Compound was evaluated to inhibit human nonpancreatic secretory Phospholipase A2 through chromogenic assay	ic50	0.0280	uM

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
Decitabine	increases expression, increases reaction, decreases reaction, affects expression, decreases methylation	3
Tetrachlorodibenzodioxin	increases expression	3
Cyclosporine	decreases methylation, decreases expression	3
sodium arsenite	affects methylation, increases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases secretion, increases expression, increases reaction	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment	2
Diethylhexyl Phthalate	decreases expression	2
Lipopolysaccharides	affects cotreatment, increases expression	2
Quercetin	decreases expression, increases expression	2
Tretinoin	increases expression	2
mangiferin	decreases activity	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
periodate-oxidized adenosine	affects expression	1
ciglitazone	affects binding, increases expression	1
caffeic acid phenethyl ester	decreases reaction, increases expression, increases reaction	1
octa-2,4,6-trienoic acid	increases expression	1
kaempferol-3-O-galactoside	affects activity	1
13-cis-12-(3’-carboxyphenyl)retinoic acid	affects binding, decreases activity	1
quercetagetin	affects activity	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	decreases reaction, increases secretion	1
CGP 52608	affects binding, increases reaction	1
LY 311727	decreases activity	1
rofecoxib	affects expression	1

ChEMBL screening assays

111 unique, capped per target: 100 binding, 11 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005696	Binding	Inhibition of human synovial recombinant group 2 secretory phospholipase A2 at 10 uM by liquid scintillation counting	New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A2 and other leukocyte functions. — J Nat Prod
CHEMBL6193897	Functional	Inhibition of human PLA2G2A in recombinant human protein using Biochemical human PLA2G2A assay	Data for DCP probe BAY-439

Clinical trials (associated diseases)

309 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	PHASE4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer