ECE2

Summary

ECE2 (endothelin converting enzyme 2, HGNC:13275) is a protein-coding gene on chromosome 3q27.1, encoding Endothelin-converting enzyme 2 (P0DPD6). Converts big endothelin-1 to endothelin-1.

Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane.

Source: NCBI Gene 9718 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Alzheimer disease (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 92 total
• Druggable target: yes
• MANE Select transcript: NM_001100121

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13275
Approved symbol	ECE2
Name	endothelin converting enzyme 2
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0604, MGC2408
Ensembl gene	ENSG00000145194
Ensembl biotype	protein_coding
OMIM	610145
Entrez	9718

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000357474, ENST00000359140, ENST00000404464, ENST00000422932, ENST00000430587, ENST00000462596, ENST00000474750, ENST00000488401, ENST00000490579, ENST00000855514, ENST00000855515, ENST00000855516, ENST00000949185, ENST00000949186

RefSeq mRNA: 3 — MANE Select: NM_001100121 NM_001037324, NM_001100120, NM_001100121

CCDS: CCDS33899, CCDS43179, CCDS46969

Canonical transcript exons

ENST00000404464 — 19 exons

Exon	Start	End
ENSE00001878560	184276022	184276192
ENSE00003667270	184276481	184276567
ENSE00003815107	184291040	184291230
ENSE00003816182	184291344	184291439
ENSE00003816353	184278167	184278313
ENSE00003816926	184276892	184277027
ENSE00003817913	184292062	184293031
ENSE00003819127	184290255	184290358
ENSE00003820305	184278492	184278557
ENSE00003820975	184283785	184283973
ENSE00003821247	184287837	184287947
ENSE00003822343	184277251	184277466
ENSE00003823481	184285478	184285592
ENSE00003824605	184277925	184278049
ENSE00003824634	184290557	184290667
ENSE00003825074	184290793	184290860
ENSE00003826502	184289437	184289535
ENSE00003827570	184289641	184289718
ENSE00003829829	184284963	184285105

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 94.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4795 / max 59.3413, expressed in 1665 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40154	8.4795	1665
40157	0.2704	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	94.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.68	gold quality
cerebellar cortex	UBERON:0002129	94.65	gold quality
cerebellum	UBERON:0002037	94.61	gold quality
hypothalamus	UBERON:0001898	94.15	gold quality
nucleus accumbens	UBERON:0001882	93.67	gold quality
body of pancreas	UBERON:0001150	90.63	gold quality
caudate nucleus	UBERON:0001873	90.21	gold quality
putamen	UBERON:0001874	89.73	gold quality
substantia nigra	UBERON:0002038	88.49	gold quality
adenohypophysis	UBERON:0002196	88.41	gold quality
pituitary gland	UBERON:0000007	88.38	gold quality
brain	UBERON:0000955	87.10	gold quality
amygdala	UBERON:0001876	86.13	gold quality
temporal lobe	UBERON:0001871	86.06	gold quality
right frontal lobe	UBERON:0002810	85.41	gold quality
anterior cingulate cortex	UBERON:0009835	84.43	gold quality
pancreas	UBERON:0001264	83.73	gold quality
primary visual cortex	UBERON:0002436	83.22	gold quality
frontal cortex	UBERON:0001870	83.18	gold quality
Ammon’s horn	UBERON:0001954	82.46	gold quality
cerebral cortex	UBERON:0000956	82.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.17	gold quality
prefrontal cortex	UBERON:0000451	81.89	gold quality
superior frontal gyrus	UBERON:0002661	81.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.01	gold quality
islet of Langerhans	UBERON:0000006	71.55	gold quality
right atrium auricular region	UBERON:0006631	65.94	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	8.88
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting ECE2, 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-3667-3P	99.99	67.17	1636
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-4462	95.10	66.27	172

Literature-anchored findings (GeneRIF, showing 9)

• The most significantly downregulated gene in this data set was the endothelin converting enzyme 2 (ECE2), implicated in amyloid beta clearance. (PMID:17188679)
• Data show that CD133 and ECE expressions are associated with lymphoid metastasis and prognosis of NSCLC, and their overexpression often suggests unfavorable prognosis of NSCLC. (PMID:17545092)
• An intact SAM-dependent methyltransferase fold is encoded by the human endothelin-converting enzyme-2 gene (PMID:19089949)
• Abeta accumulation in Alzheimer’s disease is unlikely to be caused by ECE-2 deficiency. However, ECE-2 expression is up-regulated (PMID:19541930)
• The PL405 assay is thus the first tool to study ECE-2 inhibition using high throughput screening or for ex vivo ECE-2 quantification. (PMID:20807771)
• Te results of this study suggested taht genetic variations in MMEL1, ECE1, ECE2, AGER, PLG, PLAT, NR1H3, MMP3, LRP1, TTR, NR1H2, and MMP9 genes do not play major role among the Finnish AD patient cohort. (PMID:22027013)
• ECE-2 and ECE-1 levels are significantly reduced in post-mortem brain from dementia with Lewy body patients. (PMID:28171705)
• this is the first report of ECE-2 being an autoantigen in humans. We have identified ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution. (PMID:28557628)
• Identification of Alzheimer’s disease-associated rare coding variants in the ECE2 gene. (PMID:32102983)

Cross-species orthologs

25 orthologs

Organism	Symbol	Gene ID
danio_rerio	ece2b	ENSDARG00000102142
mus_musculus	Ece2	ENSMUSG00000022842
rattus_norvegicus	Ece2	ENSRNOG00000001715
drosophila_melanogaster	Nepl21	FBGN0027578
drosophila_melanogaster	Nep3	FBGN0031081
drosophila_melanogaster	Nepl3	FBGN0031678
drosophila_melanogaster	Nepl12	FBGN0037727
drosophila_melanogaster	Nep4	FBGN0038818
drosophila_melanogaster	Nepl15	FBGN0039024
drosophila_melanogaster	Nep7	FBGN0039564
drosophila_melanogaster	Nepl18	FBGN0039611
drosophila_melanogaster	Nepl19	FBGN0039612
drosophila_melanogaster	Nepl20	FBGN0039613
caenorhabditis_elegans		WBGENE00013785
caenorhabditis_elegans		WBGENE00013786
caenorhabditis_elegans		WBGENE00013926
caenorhabditis_elegans		WBGENE00016778
caenorhabditis_elegans		WBGENE00016896
caenorhabditis_elegans		WBGENE00017550
caenorhabditis_elegans		WBGENE00017553
caenorhabditis_elegans		WBGENE00017554
caenorhabditis_elegans		WBGENE00017555
caenorhabditis_elegans		WBGENE00018196
caenorhabditis_elegans		WBGENE00018227
caenorhabditis_elegans		WBGENE00020293

Paralogs (6): PHEX (ENSG00000102174), ECE1 (ENSG00000117298), MMEL1 (ENSG00000142606), ECEL1 (ENSG00000171551), MME (ENSG00000196549), KEL (ENSG00000197993)

Protein

Protein identifiers

Endothelin-converting enzyme 2 — P0DPD6 (reviewed: P0DPD6)

All UniProt accessions (3): P0DPD6, F8WCL9, H0Y5G8

UniProt curated annotations — full annotation on UniProt →

Function. Converts big endothelin-1 to endothelin-1. Also involved in the processing of various neuroendocrine peptides, including neurotensin, angiotensin I, substance P, proenkephalin-derived peptides, and prodynorphin-derived peptides. May play a role in amyloid-beta processing.

Subcellular location. Golgi apparatus membrane. Cytoplasmic vesicle. Secretory vesicle membrane.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M13 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P0DPD6-4	ECE2-1, ECE2-2C	yes
P0DPD6-2	ECE2-2, ECE-2B
P0DPD6-3	ECE2-3
P0DPD8-1	EEF1AKMT4-ECE2-1, ECE-2A

RefSeq proteins (3): NP_001032401, NP_001093590, NP_001093591* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000718	Peptidase_M13	Family
IPR008753	Peptidase_M13_N	Domain
IPR018497	Peptidase_M13_C	Domain
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR042089	Peptidase_M13_dom_2	Homologous_superfamily

Pfam: PF01431, PF05649

UniProt features (30 total): glycosylation site 9, disulfide bond 5, binding site 3, topological domain 2, splice variant 2, sequence conflict 2, active site 2, chain 1, transmembrane region 1, sequence variant 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPD6-F1	87.75	0.81

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 (2): 649; 712 (proton donor)

Ligand- & substrate-binding residues (3): 708; 648; 652

Disulfide bonds (5): 140–145, 163–796, 171–756, 227–476, 685–808

Glycosylation sites (9): 207, 211, 252, 312, 357, 424, 580, 673, 681

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors

MSigDB gene sets: 180 (showing top): MORF_RAGE, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_45, MORF_ATRX, GOBP_REGULATION_OF_HORMONE_LEVELS, MORF_ESR1, MODULE_16, GOBP_CELL_CELL_SIGNALING, MODULE_118, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_PROTEIN_MATURATION, MODULE_379, GOBP_AMIDE_METABOLIC_PROCESS, MORF_FANCG, MORF_RAP1A

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), protein processing (GO:0016485), peptide hormone processing (GO:0016486), methylation (GO:0032259), proteolysis (GO:0006508)

GO Molecular Function (9): metalloendopeptidase activity (GO:0004222), methyltransferase activity (GO:0008168), metal ion binding (GO:0046872), catalytic activity (GO:0003824), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (7): Golgi membrane (GO:0000139), plasma membrane (GO:0005886), transport vesicle membrane (GO:0030658), cytoplasmic vesicle membrane (GO:0030659), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
bounding membrane of organelle	2
cytoplasm	2
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
signaling	1
proteolysis	1
protein maturation	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
metabolic process	1
protein metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
transferase activity, transferring one-carbon groups	1
cation binding	1
molecular_function	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
Golgi apparatus	1
membrane	1
cell periphery	1
transport vesicle	1
cytoplasmic vesicle membrane	1
vesicle membrane	1
cytoplasmic vesicle	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECE2	EDN1	P05305	913
ECE2	EDN3	P14138	893
ECE2	EDNRA	P25101	870
ECE2	EDN2	P20800	821
ECE2	IDE	P14735	795
ECE2	APP	P05067	737
ECE2	EDNRB	P24530	736
ECE2	ACE	P12821	690
ECE2	KNG1	P01042	562
ECE2	PRKCE	Q02156	528
ECE2	AGT	P01019	490
ECE2	ICE1	Q9Y2F5	478
ECE2	EEF1AKMT4	P0DPD7	464
ECE2	BACE1	P56817	455
ECE2	BET1	O15155	454

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ECE2	KDM1A	psi-mi:“MI:0914”(association)	0.350
ECE2	PI4KAP2	psi-mi:“MI:0914”(association)	0.350
LCOR	ECE2	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A0B4K692, A5HUI5, B2RQR8, D3UW23, F1N476, O16796, O44857, O95672, P07861, P08049, P08473, P0C1T0, P0DPD6, P0DPD9, P15144, P15145, P15684, P16406, P42891, P42892, P42893, P50123, P97739, Q07075, Q10715, Q10751, Q18673, Q22523, Q32LQ0, Q495T6, Q4PZA2, Q56H28, Q56NL1, Q58DD0, Q5EGZ1, Q5RE69, Q5RFN1, Q61391, Q6Q4G4, Q8IS64

Diamond homologs: A0A0B4K692, B2RQR8, F1N476, O16796, O44857, O95672, P07861, P08049, P08473, P0C1T0, P0DPD6, P0DPD8, P0DPD9, P0DPE2, P42891, P42892, P42893, P70669, P78562, P97739, Q18673, Q22523, Q495T6, Q4PZA2, Q5RE69, Q61391, Q8IS64, Q8T062, Q9JHL3, Q9JLI3, Q9JMI0, Q9W436, Q9W5Y0, W4VS99, P23276, Q9EQF2, P19621, A5PK19, A5WVX1, P0DPD7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2859 predictions. Top by Δscore:

Variant	Effect	Δscore
3:184277250:GACCC:G	acceptor_gain	1.0000
3:184277462:GCTTG:G	donor_gain	1.0000
3:184277463:CTTGG:C	donor_loss	1.0000
3:184277464:TTGGT:T	donor_loss	1.0000
3:184277465:TGG:T	donor_loss	1.0000
3:184277466:GGT:G	donor_loss	1.0000
3:184277467:G:GG	donor_gain	1.0000
3:184277467:G:T	donor_loss	1.0000
3:184277468:T:G	donor_loss	1.0000
3:184277920:CACA:C	acceptor_loss	1.0000
3:184277922:CA:C	acceptor_loss	1.0000
3:184277923:A:AG	acceptor_gain	1.0000
3:184277923:AGA:A	acceptor_loss	1.0000
3:184277924:G:GG	acceptor_gain	1.0000
3:184277924:GAA:G	acceptor_gain	1.0000
3:184277924:GAAA:G	acceptor_gain	1.0000
3:184278046:GAAG:G	donor_gain	1.0000
3:184278047:AAGGT:A	donor_loss	1.0000
3:184278048:AGG:A	donor_loss	1.0000
3:184278049:GGTAG:G	donor_loss	1.0000
3:184278050:G:GG	donor_gain	1.0000
3:184278050:GT:G	donor_loss	1.0000
3:184278051:T:A	donor_loss	1.0000
3:184278163:A:AG	acceptor_gain	1.0000
3:184278164:T:G	acceptor_gain	1.0000
3:184278164:TAGA:T	acceptor_loss	1.0000
3:184278165:A:AG	acceptor_gain	1.0000
3:184278165:AGATT:A	acceptor_gain	1.0000
3:184278166:G:GT	acceptor_gain	1.0000
3:184278166:GA:G	acceptor_gain	1.0000

AlphaMissense

5031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:184290558:T:A	W599R	1.000
3:184290558:T:C	W599R	1.000
3:184290560:G:C	W599C	1.000
3:184290560:G:T	W599C	1.000
3:184290634:T:C	L624P	1.000
3:184290834:A:T	E649V	1.000
3:184290835:G:C	E649D	1.000
3:184290835:G:T	E649D	1.000
3:184290842:C:G	H652D	1.000
3:184291190:A:T	E708V	1.000
3:184291194:C:A	N709K	1.000
3:184291194:C:G	N709K	1.000
3:184291202:A:T	D712V	1.000
3:184277362:G:A	C171Y	0.999
3:184277362:G:T	C171F	0.999
3:184277363:T:G	C171W	0.999
3:184277978:T:G	Y224D	0.999
3:184278176:T:A	W251R	0.999
3:184278176:T:C	W251R	0.999
3:184283969:T:C	L380P	0.999
3:184287854:G:C	W473C	0.999
3:184287854:G:T	W473C	0.999
3:184287861:T:C	C476R	0.999
3:184287862:G:A	C476Y	0.999
3:184287863:C:G	C476W	0.999
3:184287900:G:T	G489W	0.999
3:184289497:T:A	W525R	0.999
3:184289497:T:C	W525R	0.999
3:184289499:G:C	W525C	0.999
3:184289499:G:T	W525C	0.999

dbSNP variants (sampled 300 via entrez): RS1000078792 (3:184291583 C>T), RS1000234465 (3:184282262 CA>C), RS1000292877 (3:184289907 T>A,C), RS1000359893 (3:184275916 G>T), RS1000515751 (3:184274031 C>T), RS1000895876 (3:184286295 G>A), RS1001186886 (3:184289989 T>A,G), RS1001359929 (3:184286129 C>T), RS1001382068 (3:184282860 G>C), RS1001516408 (3:184276414 G>A), RS1001621049 (3:184288780 T>C,G), RS1001817 (3:184277553 C>A,G,T), RS1001962919 (3:184287449 T>C), RS1002027748 (3:184288469 T>C), RS1002085052 (3:184281915 A>G)

Disease associations

OMIM: gene MIM:610145 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Alzheimer disease	Limited	Autosomal dominant

Mondo (1): Alzheimer disease (MONDO:0004975)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000880_29	Menarche (age at onset)	3.000000e-07
GCST001469_1	Major depressive disorder	5.000000e-06
GCST008129_13	Body mass index	2.000000e-12
GCST011494_94	Daytime nap	2.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0007828	daytime rest measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5465381 (PROTEIN COMPLEX), CHEMBL5890 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M13: Neprilysin

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
S136492	Inhibition	5.33	pIC50
compound 1 [PMID: 18507370]	Inhibition	5.19	pIC50

ChEMBL bioactivities

6 potent at pChembl≥5 of 8 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.22	Kd	605	nM	CHEMBL4071130
5.54	IC50	2900	nM	CHEMBL4071130
5.38	Kd	4180	nM	DYNASORE
5.33	IC50	4630	nM	CHEMBL487942
5.23	IC50	5830	nM	CHEMBL487941
5.19	IC50	6420	nM	CHEMBL127545

PubChem BioAssay actives

24 with measured affinity, of 54 total; 10 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
(2S)-2-[[(2S)-2-[[hydroxy-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1799789: Enzymatic Assay from Article 10.1074/jbc.M110.120576: “Identification of an endothelin-converting enzyme-2-specific fluorigenic substrate and development of an in vitro and ex vivo enzymatic assay.”	ki	0.0012	uM
N’-(4-chlorophenyl)sulfonyl-N-(4-cyano-5-methyl-1H-pyrazol-3-yl)carbamimidate	1802886: Enzyme Activity Assay from Article 10.1074/jbc.M113.537704: “Opioid receptor function is regulated by post-endocytic peptide processing.”	ic50	0.0050	uM
(2S)-2-[[(2R)-2-(2,3-dihydro-1H-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1799789: Enzymatic Assay from Article 10.1074/jbc.M110.120576: “Identification of an endothelin-converting enzyme-2-specific fluorigenic substrate and development of an in vitro and ex vivo enzymatic assay.”	ki	0.0077	uM
(2S)-2-[[2-(5-bromo-2,3-dihydro-1H-inden-1-yl)-3-sulfanylpropanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1799789: Enzymatic Assay from Article 10.1074/jbc.M110.120576: “Identification of an endothelin-converting enzyme-2-specific fluorigenic substrate and development of an in vitro and ex vivo enzymatic assay.”	ki	0.0223	uM
(2S)-2-[[(2R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]amino]propanoic acid	1799789: Enzymatic Assay from Article 10.1074/jbc.M110.120576: “Identification of an endothelin-converting enzyme-2-specific fluorigenic substrate and development of an in vitro and ex vivo enzymatic assay.”	ki	0.1950	uM
3-hydroxy-N-[(E)-(2,4,5-trihydroxyphenyl)methylideneamino]naphthalene-2-carboxamide	1975177: Binding affinity to human GST-tagged MUS81-ECE2 expressed in Escherichia coli BL21(DE3)Rosetta2 cells assessed as dissociation constant by Surface plasmon resonance analysis	kd	0.6050	uM
2-[(Z)-2-quinolin-2-ylethenyl]phenol	1802886: Enzyme Activity Assay from Article 10.1074/jbc.M113.537704: “Opioid receptor function is regulated by post-endocytic peptide processing.”	ic50	1.6000	uM
N-[(E)-(3,4-dihydroxyphenyl)methylideneamino]-3-hydroxynaphthalene-2-carboxamide	1975177: Binding affinity to human GST-tagged MUS81-ECE2 expressed in Escherichia coli BL21(DE3)Rosetta2 cells assessed as dissociation constant by Surface plasmon resonance analysis	kd	4.1800	uM
1-pyrrolidin-1-yl-2-quinoxalin-6-ylethanone	404719: Reduction of recombinant ECE2 activity measured by McaBk2 fluorescent substrate hydrolysis	ic50	5.8300	uM
2-[(E)-2-quinolin-2-ylethenyl]phenol	404719: Reduction of recombinant ECE2 activity measured by McaBk2 fluorescent substrate hydrolysis	ic50	6.4200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	4
Cisplatin	decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
afimoxifene	increases expression, decreases reaction	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	increases phosphorylation	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estrogens	decreases reaction, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Progesterone	decreases expression, affects cotreatment	1
Selenomethionine	affects expression	1
Gonadal Steroid Hormones	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5327667	Binding	Inhibition of human GST-tagged MUS81-ECE2 expressed in Escherichia coli BL21(DE3)Rosetta2 cells incubated for 15 mins by FRET based assay	Identification of small-molecule inhibitors of human MUS81-EME1/2 by FRET-based high-throughput screening. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1QN	Abcam HeLa ECE2 KO	Cancer cell line	Female
CVCL_SL37	HAP1 ECE2 (-) 1	Cancer cell line	Male
CVCL_SL38	HAP1 ECE2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00009191	PHASE4	COMPLETED	The Depression in Alzheimer’s Disease Study (DIADS)
NCT00009217	PHASE4	COMPLETED	Treatment of Behavioral Symptoms in Alzheimer’s Disease
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00035204	PHASE4	COMPLETED	A Study of the Effects on Sleep, Attention, and Gastrointestinal Tolerance of Galantamine and Donepezil in Patients With Alzheimer’s Disease
NCT00042172	PHASE4	COMPLETED	Treatment for Early Memory Loss
NCT00046358	PHASE4	COMPLETED	The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer’s Disease
NCT00104442	PHASE4	COMPLETED	Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease
NCT00120874	PHASE4	COMPLETED	Memantine and Comprehensive, Individualized Management of Alzheimer’s Disease and Caregiver Training
NCT00142324	PHASE4	UNKNOWN	CALM-AD
NCT00165724	PHASE4	COMPLETED	Alzheimer’s Disease Long-term Follow-up Study (ALF Study)
NCT00165750	PHASE4	TERMINATED	Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients
NCT00202124	PHASE4	COMPLETED	Double Blind Study of Trp01 in Patients With Alzheimer’s Disease
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00216515	PHASE4	COMPLETED	The Efficacy of Galantamine on the Attention and the Frontal Function of the Patients With Dementia of Alzheimer Type
NCT00230568	PHASE4	COMPLETED	EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD)
NCT00234637	PHASE4	COMPLETED	Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00260624	PHASE4	COMPLETED	Escitalopram Treatment of Patients With Agitated Dementia
NCT00303277	PHASE4	COMPLETED	Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
NCT00305903	PHASE4	COMPLETED	Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease
NCT00306124	PHASE4	UNKNOWN	Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment
NCT00334906	PHASE4	COMPLETED	Study of Memantine in Assessment of Selected Measures of Volumetric Magnetic Resonance Imaging (MRI) and Cognition in Moderate AD (Alzheimer’s Disease)
NCT00369603	PHASE4	TERMINATED	Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00381381	PHASE4	COMPLETED	The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00401167	PHASE4	COMPLETED	Memantine for Agitation and Aggression in Severe Alzheimer’s Disease
NCT00403520	PHASE4	COMPLETED	Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers
NCT00417482	PHASE4	COMPLETED	Antipsychotic Discontinuation in Alzheimer’s Disease
NCT00443014	PHASE4	COMPLETED	The Dementia Study in Northern Norway
NCT00469456	PHASE4	COMPLETED	Effect of Memantine on Functional Communication in Patients With Alzheimer’s Disease
NCT00476008	PHASE4	COMPLETED	Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer’s Disease
NCT00477659	PHASE4	COMPLETED	Neural Correlates In Mild Alzheimer’s Disease
NCT00480870	PHASE4	COMPLETED	The Effect of Anticholinesterase Drugs on Sleep in Alzheimer’s Disease Patients
NCT00495820	PHASE4	COMPLETED	Methylphenidate for Apathy in Alzheimer’s Dementia: A Controlled Study
NCT00523666	PHASE4	UNKNOWN	Diffusion Tensor Weighted MRI in Alzheimer’s Disease Modifying Treatment Effects of Galantamine (Reminyl®)
NCT00549601	PHASE4	COMPLETED	Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer’s Disease
NCT00551161	PHASE4	COMPLETED	Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer’s Disease
NCT00561392	PHASE4	COMPLETED	Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer’s Disease