CTSE

Summary

CTSE (cathepsin E, HGNC:2530) is a protein-coding gene on chromosome 1q32.1, encoding Cathepsin E (P14091). May have a role in immune function.

This gene encodes a member of the A1 family of peptidases. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme, an aspartic endopeptidase, may be involved in antigen processing and the maturation of secretory proteins. Elevated expression of this gene has been observed in neurodegeneration.

Source: NCBI Gene 1510 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 94 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001910

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2530
Approved symbol	CTSE
Name	cathepsin E
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196188
Ensembl biotype	protein_coding
OMIM	116890
Entrez	1510

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000358184, ENST00000360218, ENST00000468617, ENST00000486757, ENST00000677780, ENST00000677924, ENST00000678285, ENST00000678498, ENST00000678712, ENST00000966017

RefSeq mRNA: 3 — MANE Select: NM_001910 NM_001317331, NM_001910, NM_148964

CCDS: CCDS73012, CCDS73013

Canonical transcript exons

ENST00000358184 — 9 exons

Exon	Start	End
ENSE00001399754	206012508	206012649
ENSE00001412641	206021049	206021167
ENSE00001413782	206022901	206023057
ENSE00001416095	206013772	206013894
ENSE00001660589	206009264	206010347
ENSE00001823596	206023724	206023895
ENSE00002285773	206022150	206022267
ENSE00003513818	206012308	206012406
ENSE00003633707	206015931	206016130

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 99.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0106 / max 587.3852, expressed in 93 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17057	0.5063	57
17063	0.1697	34
17059	0.1221	24
17060	0.0570	15
17062	0.0470	13
17055	0.0345	8
17056	0.0322	14
17061	0.0212	8
17058	0.0206	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.08	gold quality
duodenum	UBERON:0002114	97.09	gold quality
visceral pleura	UBERON:0002401	94.41	gold quality
pylorus	UBERON:0001166	94.06	gold quality
pancreatic ductal cell	CL:0002079	93.67	gold quality
epithelial cell of pancreas	CL:0000083	90.47	gold quality
trabecular bone tissue	UBERON:0002483	90.08	gold quality
mucosa of stomach	UBERON:0001199	89.89	gold quality
lower lobe of lung	UBERON:0008949	89.86	gold quality
rectum	UBERON:0001052	89.81	gold quality
stomach	UBERON:0000945	89.70	gold quality
body of stomach	UBERON:0001161	88.98	gold quality
upper lobe of lung	UBERON:0008948	88.53	gold quality
upper lobe of left lung	UBERON:0008952	88.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.70	gold quality
epithelium of nasopharynx	UBERON:0001951	86.56	gold quality
colonic mucosa	UBERON:0000317	86.47	gold quality
gall bladder	UBERON:0002110	86.46	gold quality
cardia of stomach	UBERON:0001162	86.14	gold quality
ileal mucosa	UBERON:0000331	85.87	gold quality
bone marrow	UBERON:0002371	85.61	gold quality
islet of Langerhans	UBERON:0000006	85.18	gold quality
lung	UBERON:0002048	85.16	gold quality
pleura	UBERON:0000977	81.40	gold quality
fundus of stomach	UBERON:0001160	80.31	gold quality
bone marrow cell	CL:0002092	79.54	gold quality
vermiform appendix	UBERON:0001154	79.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.28	gold quality
jejunum	UBERON:0002115	78.81	gold quality
mucosa of transverse colon	UBERON:0004991	78.75	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	648.10
E-GEOD-125970	yes	353.46
E-CURD-112	yes	42.82
E-MTAB-6386	no	17.69
E-HCAD-10	no	1.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, GATA1, NKX3-1, NR1I3, PPARD, SP1, SPI1, YY1

miRNA regulators (miRDB)

49 targeting CTSE, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-3978	99.24	68.39	2201

Literature-anchored findings (GeneRIF, showing 21)

• These results suggest the possible involvement of cathepsin E in disruption of the structural and functional integrity of alpha 2-macroglobulin in the endolysosome system. (PMID:12631277)
• Reduced expression of cathepsin E is observed in erythrocytes of humans with atopic dermatitis. (PMID:14769879)
• crystal structure of an activation intermediate of cathepsin E at 2.35A resolution (PMID:15342244)
• Both cathepsin E message and protein are found in human dendritic cells, but are absent in monocytes. (PMID:15699105)
• Three-dimensional structure of cathepsin-E. (PMID:15845357)
• the human cathepsin E gene is regulated by the constitutive androstane receptor (PMID:17888866)
• cathepsin E differentially regulates the nature and function of dendritic cells and macrophages (PMID:17947645)
• cathepsin E plays a substantial role in host defense against tumor cells through TRAIL-dependent apoptosis and/or tumor-associated macrophage-mediated cytotoxicity (PMID:18006832)
• CatE is important in the processing of tetanus toxin C-fragment in primary human B cells. (PMID:18996084)
• This study demonstrates the over-expression in CTSE, in particular, and TFF1 in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas. (PMID:19172291)
• Cath E selectivity was established by having -Leu**Pro- residues at the scissile peptide bond. (PMID:20600629)
• Emerging roles of cathepsin E in immune system cells and skin keratinocytes, and in host defense against cancer cells. (PMID:21664991)
• Cath E activity is useful as a potential molecular target for Pancreatic ductal adenocarcinoma and early detection imaging. (PMID:22068166)
• A comparative structure model of splice variant 2 was computed based on its alignment to the known structure of cathepsin E intermediate (Protein Data Bank code 1TZS) and used to rationalize its conformational properties and loss of activity. (PMID:22718633)
• CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis. (PMID:23451082)
• data demonstrate that CatE contributes to normal growth and development of mammary glands through proper trafficking and secretion of Wnt5a (PMID:24242330)
• Decreased activity of cathepsin E produced by decidual macrophages might be responsible for the induction of miscarriages in some recurrent miscarriage patients. (PMID:24464956)
• Cathepsin E, mitochondrial fission, and caspase activation/apoptosis are linked in the pathogenesis of pulmonary emphysema. (PMID:25239563)
• High Expression of Cathepsin E is associated with Tissues but Not Blood of Patients with Barrett’s Esophagus and Adenocarcinoma. (PMID:25348778)
• Higher contents of cathepsin A, D, and E in the wall of the aortic aneurysms and a positive correlation between the concentration of cathepsin A and D and the width of the aneurysmal widening, suggests the participation of these enzymes in the pathogenesis of the aneurysm. (PMID:30278264)
• Microglial cathepsin E plays a role in neuroinflammation and amyloid beta production in Alzheimer’s disease. (PMID:35181976)

Cross-species orthologs

24 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ctse	ENSMUSG00000004552
rattus_norvegicus	Ctse	ENSRNOG00000006963
drosophila_melanogaster	Pgcl	FBGN0011822
drosophila_melanogaster	Bace	FBGN0032049
drosophila_melanogaster	CG6508	FBGN0032303
drosophila_melanogaster	CG17134	FBGN0032304
drosophila_melanogaster	CG10104	FBGN0033933
drosophila_melanogaster	CG17283	FBGN0038505
drosophila_melanogaster	CG5860	FBGN0038506
drosophila_melanogaster	CG5863	FBGN0038507
drosophila_melanogaster	CG31661	FBGN0051661
drosophila_melanogaster	CG31926	FBGN0051926
drosophila_melanogaster	CG31928	FBGN0051928
drosophila_melanogaster	CG33128	FBGN0053128
caenorhabditis_elegans		WBGENE00000214
caenorhabditis_elegans		WBGENE00000218
caenorhabditis_elegans		WBGENE00012681
caenorhabditis_elegans		WBGENE00012682
caenorhabditis_elegans		WBGENE00012683
caenorhabditis_elegans		WBGENE00013973
caenorhabditis_elegans		WBGENE00017678
caenorhabditis_elegans		WBGENE00019104
caenorhabditis_elegans		WBGENE00019105
caenorhabditis_elegans		WBGENE00077655

Paralogs (9): PGC (ENSG00000096088), CTSD (ENSG00000117984), NAPSA (ENSG00000131400), REN (ENSG00000143839), BACE2 (ENSG00000182240), BACE1 (ENSG00000186318), PGA4 (ENSG00000229183), PGA3 (ENSG00000229859), PGA5 (ENSG00000256713)

Protein

Protein identifiers

Cathepsin E — P14091 (reviewed: P14091)

All UniProt accessions (6): A0A7I2V480, A0A7I2V4C5, A0A7I2V4K7, A0A7I2V648, A0A7P0MPN9, P14091

UniProt curated annotations — full annotation on UniProt →

Function. May have a role in immune function. Probably involved in the processing of antigenic peptides during MHC class II-mediated antigen presentation. May play a role in activation-induced lymphocyte depletion in the thymus, and in neuronal degeneration and glial cell activation in the brain.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Endosome.

Tissue specificity. Expressed abundantly in the stomach, the Clara cells of the lung and activated B-lymphocytes, and at lower levels in lymph nodes, skin and spleen. Not expressed in resting B-lymphocytes.

Post-translational modifications. Glycosylated. The nature of the carbohydrate chain varies between cell types. In fibroblasts, the proenzyme contains a high mannose-type oligosaccharide, while the mature enzyme contains a complex-type oligosaccharide. In erythrocyte membranes, both the proenzyme and mature enzyme contain a complex-type oligosaccharide. Two forms are produced by autocatalytic cleavage, form I begins at Ile-54, form II begins at Thr-57.

Miscellaneous. Dubious isoform produced through aberrant splice sites.

Similarity. Belongs to the peptidase A1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P14091-1	1	yes
P14091-2	2
P14091-3	3

RefSeq proteins (3): NP_001304260, NP_001901, NP_683865 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001461	Aspartic_peptidase_A1	Family
IPR001969	Aspartic_peptidase_AS	Active_site
IPR012848	Aspartic_peptidase_N	Domain
IPR021109	Peptidase_aspartic_dom_sf	Homologous_superfamily
IPR033121	PEPTIDASE_A1	Domain

Pfam: PF00026, PF07966

Enzyme classification (BRENDA):

• EC 3.4.23.34 — cathepsin E (BRENDA: 8 organisms, 91 substrates, 67 inhibitors, 48 Km, 55 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PRO-PRO-THR-ILE-PHE-(4-NITRO)PHE-ARG-LEU	0.03–0.13	5
(7-METHOXYCOUMARIN-4-YL)ACETYL-GLY-SER-PRO-ALA-P	0.0015–0.0023	4
LYS-PRO-ILE-GLU-PHE-(4-NITRO)PHE-ARG-LEU	0.04–0.07	4
(7-METHOXYCOUMARIN-4-YL)-ACETYL-GLY-LYS-PRO-ILE-	1.27–1.91	3
BIG ET-1	0.009	2
SUBSTANCE P	0.0023–0.0039	2
(7-METHOXYCOUMARIN-4-YL)ACETYL-GLY-LYS-PRO-ILE-I	0.0032	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-GLY-LYS-PRO-ILE-L	0.0028	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-GLY-SER-SER-ALA-P	0.0024	1
(7-METHOXYCOUMARIN-4-YL)ACETYL-L-ALA-GLY-L-PHE-L	1.94	1
ACETYL-SUBSTANCE P	0.0093	1
ACETYL-SUBSTANCE P(2-11)	0.083	1
ACETYL-SUBSTANCE P(3-11)	0.4	1
ACIDIC FIBROBLAST GROWTH FACTOR	0.143	1
BIG ET-2	0.008	1

UniProt features (57 total): strand 24, helix 11, turn 5, disulfide bond 4, splice variant 2, sequence variant 2, chain 2, active site 2, signal peptide 1, propeptide 1, mutagenesis site 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1TZS	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14091-F1	87.31	0.64

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): 96; 281

Disulfide bonds (4): 272–276, 314–351, 60, 109–114

Glycosylation sites (1): 90

Mutagenesis-validated functional residues (1):

Position	Phenotype
60	abolishes homodimerization.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 192 (showing top): MODULE_172, MODULE_92, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GNF2_PRDX2, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, KEGG_LYSOSOME, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, RODRIGUES_NTN1_TARGETS_DN, GNF2_ANK1, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GATA6_01, ICHIBA_GRAFT_VERSUS_HOST_DISEASE_35D_DN, GNF2_SPTA1, LIAN_NEUTROPHIL_GRANULE_CONSTITUENTS

GO Biological Process (2): proteolysis (GO:0006508), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886)

GO Molecular Function (4): aspartic-type endopeptidase activity (GO:0004190), peptidase activity (GO:0008233), identical protein binding (GO:0042802), hydrolase activity (GO:0016787)

GO Cellular Component (1): endosome (GO:0005768)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
antigen processing and presentation of exogenous peptide antigen	1
antigen processing and presentation of peptide antigen via MHC class II	1
endopeptidase activity	1
aspartic-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
protein binding	1
catalytic activity	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1112 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTSE	LAMP2	P13473	677
CTSE	CTSS	P25774	677
CTSE	LAMP1	P11279	612
CTSE	CTSB	P07858	565
CTSE	CTSL	P07711	527
CTSE	SCARB2	Q14108	525
CTSE	VSIG1	Q86XK7	515
CTSE	CTSC	P53634	513
CTSE	CTSZ	Q9UBR2	510
CTSE	ANXA10	Q9UJ72	506
CTSE	CTSA	P10619	461
CTSE	SIM2	Q14190	460
CTSE	CTSF	Q9UBX1	459
CTSE	CTSG	P08311	449
CTSE	CTSH	P09668	448

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CTSE	CHEK1	psi-mi:“MI:0914”(association)	0.350
CTSE	L1CAM	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
CTSE	BAG6	psi-mi:“MI:0915”(physical association)	0.000
EMG1	CTSE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): MTMR9 (Affinity Capture-MS), KCTD6 (Affinity Capture-MS), MTMR6 (Affinity Capture-MS), CCNT1 (Affinity Capture-MS), B3GALTL (Affinity Capture-MS), CHEK1 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), CTSE (Synthetic Lethality), BAG6 (Two-hybrid), CTSE (Affinity Capture-MS), MTMR6 (Affinity Capture-MS), B3GALTL (Affinity Capture-MS), CCNT1 (Affinity Capture-MS), KCTD6 (Affinity Capture-MS), CHEK1 (Affinity Capture-MS)

ESM2 similar proteins: O09043, O93428, O96009, P00794, P00795, P00796, P00797, P04073, P06281, P07339, P08424, P14091, P16228, P16476, P18242, P18276, P24268, P25796, P27823, P40782, P42210, P42211, P43159, P52115, P60016, P70269, P80209, P83493, P83495, Q05744, Q18DC8, Q18DC9, Q21966, Q28057, Q28389, Q28755, Q29078, Q29079, Q29432, Q4LAL9

Diamond homologs: A0A509AI82, A0A509AWX2, C5FS55, D4B385, D4DEN7, O09043, O42630, O76856, O93428, O96009, P00791, P00792, P00793, P00794, P00795, P00796, P00797, P03954, P03955, P04073, P06281, P07267, P07339, P08424, P0DJD7, P0DJD8, P0DJD9, P10977, P11489, P14091, P16228, P16476, P18242, P18276, P20142, P24268, P25796, P27677, P27678, P27821

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CTSE	“down-regulates quantity by destabilization”	A2M	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1045 predictions. Top by Δscore:

Variant	Effect	Δscore
1:206012405:G:GG	acceptor_gain	1.0000
1:206012405:GT:G	acceptor_gain	1.0000
1:206012405:GTA:G	acceptor_gain	1.0000
1:206012405:GTAT:G	acceptor_gain	1.0000
1:206012405:GTATG:G	acceptor_gain	1.0000
1:206012406:A:AG	acceptor_gain	1.0000
1:206012406:AGTAT:A	acceptor_gain	1.0000
1:206012413:G:A	acceptor_gain	1.0000
1:206012505:G:GG	donor_gain	1.0000
1:206012508:GAA:G	donor_gain	1.0000
1:206013769:G:GG	donor_gain	1.0000
1:206022147:G:GG	donor_gain	1.0000
1:206022150:GCA:G	donor_gain	1.0000
1:206022898:G:GG	donor_gain	1.0000
1:206022901:G:T	donor_gain	1.0000
1:206022901:GAT:G	donor_gain	1.0000
1:206022901:GATG:G	donor_gain	1.0000
1:206022902:GGAT:G	donor_gain	1.0000
1:206022921:A:T	donor_gain	1.0000
1:206022922:G:GT	donor_gain	1.0000
1:206023056:GG:G	acceptor_gain	1.0000
1:206023056:GGGT:G	acceptor_gain	1.0000
1:206023057:AG:A	acceptor_gain	1.0000
1:206023721:GTGAG:G	donor_loss	1.0000
1:206010346:G:GG	acceptor_gain	0.9900
1:206010347:A:AG	acceptor_gain	0.9900
1:206010348:CAG:C	acceptor_loss	0.9900
1:206010350:CACAG:C	acceptor_loss	0.9900
1:206010351:CCACA:C	acceptor_loss	0.9900
1:206012304:T:A	donor_loss	0.9900

AlphaMissense

2601 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:206022205:G:C	D96E	0.999
1:206022205:G:T	D96E	0.999
1:206022206:T:A	D96V	0.999
1:206010262:C:A	G371V	0.998
1:206010272:A:G	W368R	0.998
1:206010272:A:T	W368R	0.998
1:206012588:C:A	G283W	0.998
1:206013789:C:A	W256C	0.998
1:206013789:C:G	W256C	0.998
1:206013791:A:G	W256R	0.998
1:206013791:A:T	W256R	0.998
1:206022186:A:G	W103R	0.998
1:206022186:A:T	W103R	0.998
1:206022206:T:G	D96A	0.998
1:206010228:A:C	F382L	0.997
1:206010228:A:T	F382L	0.997
1:206010230:A:G	F382L	0.997
1:206010263:C:A	G371W	0.997
1:206012592:G:C	D281E	0.997
1:206012592:G:T	D281E	0.997
1:206012593:T:A	D281V	0.997
1:206012594:C:G	D281H	0.997
1:206016050:A:C	F181L	0.997
1:206016050:A:T	F181L	0.997
1:206016052:A:G	F181L	0.997
1:206016066:A:C	F176C	0.997
1:206016089:A:C	S168R	0.997
1:206016089:A:T	S168R	0.997
1:206016091:T:G	S168R	0.997
1:206021096:A:G	Y139H	0.997

dbSNP variants (sampled 300 via entrez): RS1000034488 (1:206025202 C>A), RS1000120987 (1:206024091 C>A), RS1000134354 (1:206020195 A>G), RS1000407214 (1:206024930 G>A), RS1000606361 (1:206021186 C>A,T), RS1000818101 (1:206013466 C>T), RS1001205419 (1:206025624 A>G,T), RS1001388311 (1:206020812 C>G), RS1001480818 (1:206014166 C>G,T), RS1001804055 (1:206008936 G>A), RS1001824478 (1:206015498 T>C), RS1003398918 (1:206023199 G>A,T), RS1003472813 (1:206022074 T>A), RS1003496484 (1:206016951 T>C), RS1003802586 (1:206011659 C>T)

Disease associations

OMIM: gene MIM:116890 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3092 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,607 (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
CHEMBL222559	TIPRANAVIR	4	17,513
CHEMBL296588	PEPSTATIN	2	26,094

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — A1: Pepsin

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

Ligand	Action	Affinity	Parameter
compound 2 [PMID: 8410973]	Inhibition	10.0	pKi
compound 3 [PMID: 8410973]	Inhibition	9.3	pKi
grassystatin A	Inhibition	9.05	pIC50
grassystatin G	Inhibition	6.88	pIC50

Binding affinities (BindingDB)

10 measured of 10 human assays (10 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[3-[(3-chloro-6-fluoroquinolin-8-yl)amino]phenyl]-5-methyl-2,6-dihydro-1,4-oxazin-3-amine	IC50	250 nM	US-9242943: 1,4 oxazines as BACE1 and/or BACE2 inhibitors
(5R)-5-[5-[[3-(difluoromethoxy)quinolin-8-yl]amino]-2-fluorophenyl]-5-methyl-2,6-dihydro-1,4-oxazin-3-amine	IC50	270 nM	US-9242943: 1,4 oxazines as BACE1 and/or BACE2 inhibitors
2-amino-3-cyclohexyl-5-phenyl-5-(3-pyridin-3-ylphenyl)imidazol-4-one	IC50	1680 nM	US-9353089: Compositions and methods for the treatment of malaria
2-amino-5,5-bis(4-methoxyphenyl)-3-(oxan-4-ylmethyl)imidazol-4-one	IC50	2070 nM	US-9353089: Compositions and methods for the treatment of malaria
2-amino-5,5-diphenyl-3-(2-phenylbutyl)imidazol-4-one	IC50	2300 nM	US-9353089: Compositions and methods for the treatment of malaria
tert-butyl 4-[2-amino-4,4-bis(4-methoxyphenyl)-5-oxoimidazol-1-yl]piperidine-1-carboxylate	IC50	6010 nM	US-9353089: Compositions and methods for the treatment of malaria
2-amino-3-cyclohexyl-5-(4-methoxyphenyl)-5-(3-pyridin-3-ylphenyl)imidazol-4-one	IC50	7150 nM	US-9353089: Compositions and methods for the treatment of malaria
2-amino-5,5-bis(4-methoxyphenyl)-3-(oxan-4-yl)imidazol-4-one	IC50	10000 nM	US-9353089: Compositions and methods for the treatment of malaria
2-amino-3-cyclohexyl-5,5-bis(4-methoxyphenyl)imidazol-4-one	IC50	12000 nM	US-9353089: Compositions and methods for the treatment of malaria
2-amino-3-cyclohexyl-5,5-bis(3-methoxyphenyl)imidazol-4-one	IC50	28900 nM	US-9353089: Compositions and methods for the treatment of malaria

ChEMBL bioactivities

112 potent at pChembl≥5 of 118 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	PEPSTATIN
10.00	IC50	0.1	nM	PEPSTATIN
10.00	Ki	0.1	nM	CHEMBL313773
9.74	IC50	0.181	nM	PEPSTATIN
9.52	IC50	0.3	nM	SYMPLOCIN A
9.52	IC50	0.3	nM	PEPSTATIN
9.45	IC50	0.354	nM	GRASSYSTATIN B
9.40	IC50	0.4	nM	GRASSYSTATIN B
9.40	IC50	0.4	nM	CHEMBL595066
9.35	IC50	0.446	nM	PEPSTATIN
9.30	IC50	0.5	nM	CHEMBL4163078
9.30	Ki	0.5	nM	CHEMBL88415
9.30	Ki	0.5	nM	CHEMBL287423
9.14	IC50	0.724	nM	CHEMBL2181022
9.10	IC50	0.8	nM	GRASSYSTATIN A
9.05	IC50	0.9	nM	GRASSYSTATIN A
9.05	IC50	0.886	nM	GRASSYSTATIN A
8.72	IC50	1.92	nM	CHEMBL2181024
8.70	Ki	2	nM	CHEMBL507651
8.70	Ki	2	nM	CHEMBL84970
8.66	Ki	2.2	nM	CHEMBL87025
8.54	Ki	2.9	nM	CHEMBL88526
8.52	Ki	3	nM	CHEMBL167514
8.48	Ki	3.3	nM	CHEMBL88356
8.40	IC50	4	nM	CHEMBL600326
8.31	IC50	4.94	nM	CHEMBL2181021
8.30	IC50	5	nM	CHEMBL4170992
8.30	Ki	5	nM	CHEMBL270359
8.30	IC50	5	nM	PEPSTATIN
8.30	IC50	5	nM	CHEMBL595267
8.10	IC50	8	nM	CHEMBL589369
8.05	IC50	9	nM	CHEMBL2181015
8.05	IC50	9	nM	CHEMBL4167618
7.96	Ki	11	nM	CHEMBL316095
7.92	IC50	12.04	nM	CHEMBL5184529
7.82	Ki	15	nM	CHEMBL418948
7.77	Ki	17	nM	CHEMBL62380
7.68	IC50	20.8	nM	CHEMBL2181018
7.68	Ki	21	nM	CHEMBL88340
7.64	IC50	23	nM	CHEMBL3813928
7.64	IC50	23	nM	CHEMBL4159706
7.62	Ki	24	nM	CHEMBL403727
7.58	Ki	26	nM	CHEMBL6191875
7.52	IC50	30.4	nM	CHEMBL2181019
7.52	IC50	30	nM	CHEMBL4173516
7.52	Ki	30	nM	CHEMBL509210
7.44	IC50	36.4	nM	CHEMBL2181011
7.43	IC50	37.5	nM	TASIAMIDE B
7.37	IC50	43	nM	CHEMBL4174823
7.37	IC50	42.9	nM	GRASSYSTATIN C

PubChem BioAssay actives

98 with measured affinity, of 171 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
(3R,4S)-5-cyclohexyl-2,2-difluoro-3-hydroxy-N-[(2S)-2-methylbutyl]-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]pentanamide	48191: Binding affinity against human cathepsin E	ki	0.0001	uM
(3S,4S)-3-hydroxy-4-[[(2S)-2-[[(3S,4S)-3-hydroxy-6-methyl-4-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-methylbutanoylamino)butanoyl]amino]butanoyl]amino]heptanoyl]amino]propanoyl]amino]-6-methylheptanoic acid	1305442: Inhibition of human recombinant cathepsin E using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition measured every 5 mins for 120 mins by fluorescence analysis	ic50	0.0001	uM
methyl (2S)-1-[(2R)-2-[[2-[[(2S)-2-[[(3R,4S)-4-[[(2S)-2-[[(2S)-2-[[(2R)-2-[(2R,3R)-2-(dimethylamino)-3-methylpentanoyl]oxy-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylbutanoyl]amino]acetyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	657936: Inhibition of cathepsin E	ic50	0.0003	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-2-[[(3S,4S)-4-[[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[(2S)-2-[(2S)-2-(dimethylamino)-3-methylbutanoyl]oxy-3-methylbutanoyl]oxy-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-hydroxybutanoyl]amino]butanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1493088: Inhibition of recombinant human C-terminal His10-tagged cathepsin E (Gln18 to Pro396 residues) using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 15 mins followed by substrate addition measured at 5 mins interval for 120 mins by fluorescence assay	ic50	0.0004	uM
(4S)-4-[(1R)-1-hydroxy-2-[[1-(3-propan-2-ylphenyl)cyclopropyl]amino]ethyl]-19-(methoxymethyl)-11-oxa-3,16-diazatricyclo[15.3.1.16,10]docosa-1(21),6(22),7,9,17,19-hexaen-2-one	453188: Inhibition of cathepsin E	ic50	0.0004	uM
(4S)-5-cyclohexyl-2,2-difluoro-N-(2-morpholin-4-ylethyl)-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]-3-oxopentanamide	48191: Binding affinity against human cathepsin E	ki	0.0005	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[(2S)-2-(dimethylamino)-3-phenylpropanoyl]oxypropanoyl]amino]-4-methylpentanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1493088: Inhibition of recombinant human C-terminal His10-tagged cathepsin E (Gln18 to Pro396 residues) using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 15 mins followed by substrate addition measured at 5 mins interval for 120 mins by fluorescence assay	ic50	0.0005	uM
(4S)-5-cyclohexyl-2,2-difluoro-N-[(2S)-2-methylbutyl]-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]-3-oxopentanamide	48191: Binding affinity against human cathepsin E	ki	0.0005	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[methyl-[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1901891: Inhibition of Cathepsin E (unknown origin) using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay	ic50	0.0007	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-2-[[(3S,4S)-4-[[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[(2S)-2-[(2S)-2-(dimethylamino)-3-methylbutanoyl]oxy-3-methylbutanoyl]oxy-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	674496: Inhibition of cathepsin E using MCA-KPILFFRLK(Dnp)-D-R-NH2 as substrate incubated for 10 to 15 mins prior to substrate addition measured every 5 min for 2 hrs by fluorometry	ic50	0.0008	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[methyl-[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0019	uM
1-N-[(1S,2S)-1-[(4S)-1-benzyl-5-oxoimidazolidin-4-yl]-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl]-5-methyl-3-N,3-N-dipropylbenzene-1,3-dicarboxamide	408454: Inhibition of cathepsin E	ki	0.0020	uM
(2S)-N-[(2S,3S,5S)-1-cyclohexyl-3,5-dihydroxy-6-methylheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	48191: Binding affinity against human cathepsin E	ki	0.0020	uM
(2S)-N-[(2S,3S,5S)-1-cyclohexyl-5-(1,3-dithian-2-yl)-3,5-dihydroxypentan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	48191: Binding affinity against human cathepsin E	ki	0.0022	uM
(2S)-N-[2-[[(2S,3S,5S)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]amino]-2-oxo-1-prop-2-enylsulfanylethyl]-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanamide	48191: Binding affinity against human cathepsin E	ki	0.0029	uM
(2S)-N-[(2S,3S,5S)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	48191: Binding affinity against human cathepsin E	ki	0.0033	uM
(4S)-4-[(1R)-1-hydroxy-2-[[1-(3-propan-2-ylphenyl)cyclopropyl]amino]ethyl]-19-methyl-11,16-dioxa-3,18-diazatricyclo[15.3.1.16,10]docosa-1(21),6(22),7,9,17,19-hexaen-2-one	453188: Inhibition of cathepsin E	ic50	0.0040	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylbutanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0049	uM
1-N-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-[(2R,4R)-4-phenylmethoxypyrrolidin-2-yl]propan-2-yl]-5-methyl-3-N,3-N-dipropylbenzene-1,3-dicarboxamide	316777: Binding affinity to human cathepsin E	ki	0.0050	uM
methyl (2S)-1-[(2R)-2-[[2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-4-methylpentanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1493088: Inhibition of recombinant human C-terminal His10-tagged cathepsin E (Gln18 to Pro396 residues) using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 15 mins followed by substrate addition measured at 5 mins interval for 120 mins by fluorescence assay	ic50	0.0050	uM
(4S)-4-[(1R)-1-hydroxy-2-[[1-(3-propan-2-ylphenyl)cyclopropyl]amino]ethyl]-19-(methoxymethyl)-11,16-dioxa-3,18-diazatricyclo[15.3.1.16,10]docosa-1(20),6(22),7,9,17(21),18-hexaen-2-one	453188: Inhibition of cathepsin E	ic50	0.0050	uM
(4S)-4-[(1R)-1-hydroxy-2-[(3-propan-2-ylphenyl)methylamino]ethyl]-19-methyl-11,16-dioxa-3,18-diazatricyclo[15.3.1.16,10]docosa-1(21),6(22),7,9,17,19-hexaen-2-one	453188: Inhibition of cathepsin E	ic50	0.0080	uM
(2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylbutanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylic acid	1493088: Inhibition of recombinant human C-terminal His10-tagged cathepsin E (Gln18 to Pro396 residues) using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 15 mins followed by substrate addition measured at 5 mins interval for 120 mins by fluorescence assay	ic50	0.0090	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylbutanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1305442: Inhibition of human recombinant cathepsin E using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition measured every 5 mins for 120 mins by fluorescence analysis	ic50	0.0090	uM
(2S)-N-[(2S,3S,5R)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	48191: Binding affinity against human cathepsin E	ki	0.0110	uM
benzyl N-[(2S)-1-[[(2S)-5-amino-1-[[(2S,3S)-5-[[(2S)-1-[[(2S)-1-[[(2R)-1-[(2S)-2-[2-[2-[2-[4-[[[(2S)-6-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[3-[(2R)-3’,3’-dimethyl-6-nitrospiro[chromene-2,2’-indole]-1’-yl]propanoylamino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[5-amino-2-[[(2S)-2-[3-[(2R)-3’,3’-dimethyl-6-nitrospiro[3,4-dihydrochromene-2,2’-indole]-1’-yl]propanoylamino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethylcarbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-methylamino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-5-oxo-1-phenylpentan-2-yl]amino]-1,5-dioxopentan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]carbamate	1901891: Inhibition of Cathepsin E (unknown origin) using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay	ic50	0.0120	uM
(2S)-N-[(2S,3S,5S)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]-6-(methylcarbamothioylamino)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]hexanamide	48191: Binding affinity against human cathepsin E	ki	0.0150	uM
(2S)-N-[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enamide	48191: Binding affinity against human cathepsin E	ki	0.0170	uM
(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylbutanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoic acid	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0208	uM
(3R,4S)-5-cyclohexyl-2,2-difluoro-3-hydroxy-N-(2-morpholin-4-ylethyl)-4-[[(2S)-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]pent-4-enoyl]amino]pentanamide	48191: Binding affinity against human cathepsin E	ki	0.0210	uM
methyl (2S)-1-[(2R)-2-[[2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylpentanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1305442: Inhibition of human recombinant cathepsin E using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition measured every 5 mins for 120 mins by fluorescence analysis	ic50	0.0230	uM
(2S)-1-[(2R)-2-[[2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylpentanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylic acid	1493088: Inhibition of recombinant human C-terminal His10-tagged cathepsin E (Gln18 to Pro396 residues) using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 15 mins followed by substrate addition measured at 5 mins interval for 120 mins by fluorescence assay	ic50	0.0230	uM
1-N-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-[(2R,4R)-4-phenoxypyrrolidin-2-yl]propan-2-yl]-5-methyl-3-N,3-N-dipropylbenzene-1,3-dicarboxamide	316777: Binding affinity to human cathepsin E	ki	0.0240	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-4-methylpentanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1493088: Inhibition of recombinant human C-terminal His10-tagged cathepsin E (Gln18 to Pro396 residues) using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 15 mins followed by substrate addition measured at 5 mins interval for 120 mins by fluorescence assay	ic50	0.0300	uM
1-N-[(1S,2S)-1-[(2S)-4-benzyl-3-oxopiperazin-2-yl]-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl]-5-methyl-3-N,3-N-dipropylbenzene-1,3-dicarboxamide	408454: Inhibition of cathepsin E	ki	0.0300	uM
(2S)-N-[(2S,3S)-5-[[(2S)-1-[[(2S)-1-[[(2R)-1-(benzylamino)-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-5-oxo-1-phenylpentan-2-yl]-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylbutanoyl]-methylamino]pentanediamide	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0304	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-3-hydroxy-4-[[3-[methyl(methylsulfonyl)amino]-5-[[(1R)-1-phenylethyl]carbamoyl]benzoyl]amino]-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0364	uM
methyl (2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylbutanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0375	uM
methyl (2S)-1-[(2R)-2-[[2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2R,3S)-2-hydroxy-3-methylpentanoyl]amino]-4-methylpentanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	448177: Inhibition of cathepsin E	ic50	0.0429	uM
methyl (2S)-1-[(2R)-2-[[2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-4-amino-2-[[(2S)-2-[[(2R,3S)-2-hydroxy-3-methylpentanoyl]amino]-4-methylpentanoyl]-methylamino]-4-oxobutanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	1493088: Inhibition of recombinant human C-terminal His10-tagged cathepsin E (Gln18 to Pro396 residues) using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 15 mins followed by substrate addition measured at 5 mins interval for 120 mins by fluorescence assay	ic50	0.0430	uM
methyl (3S)-4-[[(2S,3S,5R)-1-cyclohexyl-3,5-dihydroxyheptan-2-yl]amino]-3-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]-4-oxobutanoate	48191: Binding affinity against human cathepsin E	ki	0.0440	uM
(2S)-N-[(2S,3S)-3-hydroxy-5-[[(2S)-4-methyl-1-[[(2S)-1-[methyl-[(2R)-1-oxo-3-phenyl-1-(propan-2-ylamino)propan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-5-oxo-1-phenylpentan-2-yl]-2-[[(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-methylbutanoyl]-methylamino]pentanediamide	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0519	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-amino-3-methylbutanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0582	uM
(4S)-3’-(3,6-dihydro-2H-pyran-5-yl)-1’-fluoro-7’-(2-fluoro-3-pyridinyl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1546028: Inhibition of cathepsin E (unknown origin)	ic50	0.0750	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-2-acetamido-5-amino-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	711206: Inhibition of cathepsin E by fluorescence assay	ic50	0.0775	uM
N-[(1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-[(2R)-4-(3-methylphenyl)sulfonylpiperazin-2-yl]propan-2-yl]-3-[(2R)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-5-methylbenzamide	479464: Inhibition oh cathepsin E	ki	0.0860	uM
benzyl N-[(2S)-1-[[(2S)-5-amino-1-[[(2S,3S)-5-[[(2S)-1-[[(2S)-1-[[(2R)-1-[(2S)-2-[2-[2-[2-[4-[[[(2S)-6-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[3-[(2R)-3’,3’-dimethyl-6-nitrospiro[chromene-2,2’-indole]-1’-yl]propanoylamino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[5-amino-2-[[(2S)-2-[3-[(2R)-3’,3’-dimethyl-6-nitrospiro[3,4-dihydrochromene-2,2’-indole]-1’-yl]propanoylamino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-5-oxo-1-phenylpentan-2-yl]amino]-1,5-dioxopentan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]carbamate	1901891: Inhibition of Cathepsin E (unknown origin) using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay	ic50	0.1000	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[methyl-[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carboxylate	1901891: Inhibition of Cathepsin E (unknown origin) using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay	ic50	0.1040	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[methyl-[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]-methylamino]-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoyl]pyrrolidine-2-carboxylate	1901891: Inhibition of Cathepsin E (unknown origin) using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay	ic50	0.1050	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(1S,2S)-1-[(3S)-1-butyl-5,5-dimethyl-2-oxopyrrolidin-3-yl]-3-cyclohexyl-1-hydroxypropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	48188: Inhibitory concentration against cathepsin E	ic50	0.1150	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
lasiocarpine	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Hydrogen Peroxide	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Progesterone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Butyric Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

71 unique, capped per target: 69 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1039222	Binding	Inhibition of cathepsin E assessed as residual activity at 10 uM after 10 to 15 mins by fluorescence assay relative to control	Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. — J Med Chem
CHEMBL4343418	ADMET	Inhibition of cathepsin E (unknown origin)	Discovery of AM-6494: A Potent and Orally Efficacious β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor with in Vivo Selectivity over BACE2. — J Med Chem
CHEMBL661019	Functional	Inhibitory concentration against cathepsin E	Renin inhibitors containing conformationally restricted P1-P1’ dipeptide mimetics. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer