CTSV

Summary

CTSV (cathepsin V, HGNC:2538) is a protein-coding gene on chromosome 9q22.33, encoding Cathepsin L2 (O60911). Cysteine protease.

The protein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that may play an important role in corneal physiology. This gene is expressed in colorectal and breast carcinomas but not in normal colon, mammary gland, or peritumoral tissues, suggesting a possible role for this gene in tumor processes. Alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 1515 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001333

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2538
Approved symbol	CTSV
Name	cathepsin V
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	CTSU
Ensembl gene	ENSG00000136943
Ensembl biotype	protein_coding
OMIM	603308
Entrez	1515

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 19 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000259470, ENST00000479932, ENST00000538255, ENST00000679551, ENST00000679661, ENST00000679917, ENST00000680159, ENST00000680221, ENST00000680385, ENST00000680435, ENST00000680490, ENST00000680787, ENST00000681330, ENST00000681517, ENST00000681737, ENST00000681927, ENST00000851836, ENST00000930701, ENST00000930702, ENST00000930703, ENST00000930704, ENST00000930705, ENST00000930706, ENST00000930707, ENST00000930708, ENST00000930709, ENST00000930710, ENST00000930711

RefSeq mRNA: 2 — MANE Select: NM_001333 NM_001201575, NM_001333

CCDS: CCDS6723

Canonical transcript exons

ENST00000259470 — 8 exons

Exon	Start	End
ENSE00000926436	97029677	97033048
ENSE00000926438	97035528	97035693
ENSE00000926439	97036523	97036747
ENSE00001633766	97037252	97037398
ENSE00001781677	97034726	97034843
ENSE00001861471	97039071	97039142
ENSE00003550615	97037918	97038053
ENSE00003604079	97037493	97037615

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3102 / max 1296.1943, expressed in 935 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101612	17.3102	935

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	98.74	gold quality
upper arm skin	UBERON:0004263	98.74	gold quality
upper leg skin	UBERON:0004262	98.03	gold quality
oocyte	CL:0000023	95.97	gold quality
pigmented layer of retina	UBERON:0001782	95.93	gold quality
amniotic fluid	UBERON:0000173	93.57	gold quality
secondary oocyte	CL:0000655	93.45	gold quality
hair follicle	UBERON:0002073	92.80	gold quality
mammalian vulva	UBERON:0000997	92.43	gold quality
tongue squamous epithelium	UBERON:0006919	91.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.50	gold quality
metanephric glomerulus	UBERON:0004736	90.65	gold quality
esophagus squamous epithelium	UBERON:0006920	90.44	gold quality
epithelium of esophagus	UBERON:0001976	90.35	gold quality
buccal mucosa cell	CL:0002336	90.26	gold quality
adult organism	UBERON:0007023	89.90	gold quality
renal glomerulus	UBERON:0000074	89.77	gold quality
skin of hip	UBERON:0001554	89.06	gold quality
kidney epithelium	UBERON:0004819	87.99	gold quality
penis	UBERON:0000989	87.47	gold quality
right testis	UBERON:0004534	87.45	gold quality
zone of skin	UBERON:0000014	86.52	gold quality
testis	UBERON:0000473	86.52	gold quality
cervix epithelium	UBERON:0004801	86.34	gold quality
squamous epithelium	UBERON:0006914	86.04	gold quality
oral cavity	UBERON:0000167	85.81	gold quality
nephron tubule	UBERON:0001231	85.73	gold quality
left testis	UBERON:0004533	85.71	gold quality
skin of abdomen	UBERON:0001416	85.66	gold quality
palpebral conjunctiva	UBERON:0001812	84.80	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	7933.61
E-CURD-79	yes	578.53
E-HCAD-24	yes	183.62
E-GEOD-134144	yes	47.81
E-MTAB-8271	yes	8.93
E-MTAB-3929	no	2401.14
E-GEOD-109979	no	603.92
E-MTAB-8060	no	305.77
E-MTAB-6524	no	262.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, FOXO1, PGR

miRNA regulators (miRDB)

98 targeting CTSV, 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-8485	100.00	77.57	4731
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948

Literature-anchored findings (GeneRIF, showing 32)

• stratum corneum thiol protease is identical with the recently described cathepsin L2 protease. (PMID:12648222)
• Cathepsin V is involved in the degradation of invariant chain in human thymus (PMID:12925692)
• Cathepsin V has an elastolytic activity and is expressed in activated macrophages (PMID:15192101)
• Human cathepsin V compensates for murine cathepsin L in mouse epidermis and hair follicles. (PMID:15679121)
• Identification of CTSV & CTSL as targets for cystatin M/E, their (co)-expression in the stratum granulosum of skin, and activity of CTSL toward transglutaminase 3 strongly imply an important role for them in the differentiation process of human epidermis. (PMID:16565075)
• propeptide was found to behave as a tight-binding inhibitor against CatV (PMID:17516850)
• Associated with type 1 diabetes and early-onset myasthenia gravis. (PMID:17869649)
• angiogenesis inhibition activity on endothelial cells caused by plasminogen processing by cathepsin V (PMID:18163891)
• functions of CTSL and CTSV in the positive selection of CD4+ T cells (PMID:20347002)
• A proteolytically active variant of cathepsin V is localized to cell nucleus (in peri-nucleolar pattern) in thyroid carcinoma cells. (PMID:20536394)
• Findings indicate the unique function of cathepsin V for producing enkephalin and neuropeptide Y (NPY) neuropeptides required for neurotransmission in health and neurological diseases. (PMID:22393040)
• CTSL2 might be involved in progression of endometrial cancer. (PMID:22452389)
• inflammatory cues and monocyte-endothelial cell interactions upregulate cathepsin K and V activity via a JNK signaling axis (PMID:22562303)
• functions of cathepsin V are controlled by N-glycosylation (PMID:22967898)
• Cathepsin V expression contributes to the development of dermal fibrosis and vasculopathy in systemic sclerosis. (PMID:23287360)
• E2F1 directly binds to CTSL2 promoter and regulates CTSL2 gene expression. (PMID:23542171)
• Expression of cathepsins K, S and V within keratinocytes is reduced in photoprotected skin of aged women. (PMID:23871919)
• using cathepsin V and cathepsin L as model enzymes, a series of chimeras were generated to identify noncatalytic regions that are responsible for the potent elastolytic activity of cathepsin V (PMID:24121514)
• Cathepsins V and S may serve as auxiliary diagnostic and/or prognostic markers in thymic epithelial tumors. (PMID:27771373)
• exogenous CTSV inhibited Ang -induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR (PMID:28522343)
• The study demonstrates that change in the proportion of melanocores in the intact/undegraded state by CTSV-related degradation in keratinocytes affects photoprotection of the skin. (PMID:29623762)
• CTSV is involved in melanosome degradation. (PMID:29654760)
• CTSV protein expression increases significantly at adherent sites of extravillous trophoblasts that invade myometrium in placenta accreta cases, but expression is weak at non-adherent sites. Therefore CTSV may play a role in placenta accreta pathogenesis. (PMID:30759440)
• High expression of CTSV is associated with poor outcome in breast ductal carcinoma in situ and is a potential marker to predict DCIS progression to invasive disease. (PMID:31444238)
• Expression of elastolytic cathepsins in human skin and their involvement in age-dependent elastin degradation. (PMID:32007579)
• Significance of nuclear cathepsin V in normal thyroid epithelial and carcinoma cells. (PMID:32910988)
• HMGB1 mediates homocysteine-induced endothelial cells pyroptosis via cathepsin V-dependent pathway. (PMID:32912629)
• Cathepsin V Mediates the Tazarotene-induced Gene 1-induced Reduction in Invasion in Colorectal Cancer Cells. (PMID:32918681)
• Cathepsin V suppresses GATA3 protein expression in luminal A breast cancer. (PMID:33298139)
• Cathepsin V: Molecular characteristics and significance in health and disease. (PMID:35305807)
• CTSV (cathepsin V) promotes bladder cancer progression by increasing NF-kappaB activity. (PMID:35443863)
• Cathepsin V is correlated with the prognosis and tumor microenvironment in liver cancer. (PMID:38051285)

Cross-species orthologs

36 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctsl.1	ENSDARG00000003902
danio_rerio	zgc:103438	ENSDARG00000035663
danio_rerio	si:dkey-267n13.1	ENSDARG00000035665
danio_rerio	ctss1	ENSDARG00000036940
danio_rerio	tinagl1	ENSDARG00000061231
danio_rerio	ctsf	ENSDARG00000063095
danio_rerio	zgc:110239	ENSDARG00000077664
danio_rerio	si:zfos-1897c11.1	ENSDARG00000077910
danio_rerio	si:dkey-183k8.2	ENSDARG00000089026
danio_rerio	si:dkey-228a15.1	ENSDARG00000095698
danio_rerio	zgc:123103	ENSDARG00000099200
danio_rerio	ctsbb	ENSDARG00000101051
rattus_norvegicus	Ctsl	ENSRNOG00000018566
drosophila_melanogaster	CtsB	FBGN0030521
drosophila_melanogaster	CtsL4	FBGN0032228
drosophila_melanogaster	CtsL2	FBGN0033874
drosophila_melanogaster	Swim	FBGN0034709
drosophila_melanogaster	CtsL3	FBGN0037396
drosophila_melanogaster	CtsK1	FBGN0250848
drosophila_melanogaster	CtsF	FBGN0260462
caenorhabditis_elegans		WBGENE00000781
caenorhabditis_elegans		WBGENE00000782
caenorhabditis_elegans		WBGENE00000784
caenorhabditis_elegans		WBGENE00000785
caenorhabditis_elegans	cpz-1	WBGENE00000788
caenorhabditis_elegans		WBGENE00007055
caenorhabditis_elegans	F26E4.3	WBGENE00009158
caenorhabditis_elegans		WBGENE00013072
caenorhabditis_elegans		WBGENE00013076
caenorhabditis_elegans		WBGENE00013764
caenorhabditis_elegans		WBGENE00016300
caenorhabditis_elegans		WBGENE00016306
caenorhabditis_elegans		WBGENE00019314
caenorhabditis_elegans		WBGENE00019986
caenorhabditis_elegans		WBGENE00022189
caenorhabditis_elegans		WBGENE00044760

Paralogs (12): CTSZ (ENSG00000101160), CTSH (ENSG00000103811), CTSC (ENSG00000109861), CTSL (ENSG00000135047), TINAG (ENSG00000137251), TINAGL1 (ENSG00000142910), CTSK (ENSG00000143387), CTSS (ENSG00000163131), CTSB (ENSG00000164733), CTSW (ENSG00000172543), CTSF (ENSG00000174080), CTSO (ENSG00000256043)

Protein

Protein identifiers

Cathepsin L2 — O60911 (reviewed: O60911)

Alternative names: Cathepsin U, Cathepsin V

All UniProt accessions (6): A0A7P0T891, A0A7P0T8X8, A0A7P0T983, A0A7P0Z415, A0A804EQJ3, O60911

UniProt curated annotations — full annotation on UniProt →

Function. Cysteine protease. May have an important role in corneal physiology.

Subcellular location. Lysosome.

Tissue specificity. Predominantly expressed in the thymus and testis. Also expressed in corneal epithelium, and to a lesser extent in conjunctival epithelium and skin.

Activity regulation. Inhibited by CST6.

Similarity. Belongs to the peptidase C1 family.

RefSeq proteins (2): NP_001188504, NP_001324* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000169	Pept_cys_AS	Active_site
IPR000668	Peptidase_C1A_C	Domain
IPR013128	Peptidase_C1A	Family
IPR013201	Prot_inhib_I29	Domain
IPR025660	Pept_his_AS	Active_site
IPR025661	Pept_asp_AS	Active_site
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR039417	Peptidase_C1A_papain-like	Domain

Pfam: PF00112, PF08246

Enzyme classification (BRENDA):

• EC 3.4.22.43 — cathepsin V (BRENDA: 2 organisms, 70 substrates, 61 inhibitors, 19 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BENZYLOXYCARBONYL-PHE-ARG-7-AMIDO-4-METHYLCOUMAR	0.0044–0.0069	7
Z-PHE-ARG-4-METHYL-7-COUMARYL AMIDE	0.0041–0.0048	2
2-AMINOBENZOYL-ALRSSKQ-N-(2,4-DINITROPHENYL)ETHY	0.0016	1
2-AMINOBENZOYL-EE-EPSILON-AMINO-CAPROIC ACID-ELK	0.0017	1
2-AMINOBENZOYL-ELKLQ-N-(2,4-DINITROPHENYL)ETHYLE	0.002	1
2-AMINOBENZOYL-KK-EPSILON-AMINO-CAPROIC ACID-ELK	0.0008	1
2-AMINOBENZOYL-KLRSIKQ-N-(2,4-DINITROPHENYL)ETHY	0.0006	1
2-AMINOBENZOYL-KLRSSKQ-N-(2,4-DINITROPHENYL)ETHY	0.0012	1
2-AMINOBENZOYL-KLRVSKQ-N-(2,4-DINITROPHENYL)ETHY	0.0006	1
BENZYLOXYCARBONYL-VAL-VAL-ARG-7-AMIDO-4-METHYLCO	0.0024	1

UniProt features (37 total): strand 13, helix 9, disulfide bond 3, turn 3, active site 3, glycosylation site 2, signal peptide 1, propeptide 1, sequence conflict 1, chain 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
7QGW	X-RAY DIFFRACTION	1.3
7Q9H	X-RAY DIFFRACTION	1.4
7QHJ	X-RAY DIFFRACTION	1.4
7QNS	X-RAY DIFFRACTION	1.4
7Q8F	X-RAY DIFFRACTION	1.49
7QFF	X-RAY DIFFRACTION	1.5
7QFH	X-RAY DIFFRACTION	1.52
7Q8M	X-RAY DIFFRACTION	1.57
7Q8I	X-RAY DIFFRACTION	1.59
1FH0	X-RAY DIFFRACTION	1.6
7Q8J	X-RAY DIFFRACTION	1.64
7Q8P	X-RAY DIFFRACTION	1.71
7Q8K	X-RAY DIFFRACTION	1.74
7Q8H	X-RAY DIFFRACTION	1.75
7QO2	X-RAY DIFFRACTION	1.77
7Q8D	X-RAY DIFFRACTION	1.8
7Q8L	X-RAY DIFFRACTION	1.8
7QHK	X-RAY DIFFRACTION	1.83
7Q8O	X-RAY DIFFRACTION	1.9
7PK4	X-RAY DIFFRACTION	1.92
3KFQ	X-RAY DIFFRACTION	1.99
7Q8N	X-RAY DIFFRACTION	2
7Q8G	X-RAY DIFFRACTION	2.06
7Q8Q	X-RAY DIFFRACTION	2.13
3H6S	X-RAY DIFFRACTION	2.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60911-F1	93.13	0.86

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 (3): 138; 277; 301

Disulfide bonds (3): 270–323, 135–178, 169–211

Glycosylation sites (2): 221, 292

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1236977	Endosomal/Vacuolar pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-1679131	Trafficking and processing of endosomal TLR
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-2132295	MHC class II antigen presentation
R-HSA-8939242	RUNX1 regulates transcription of genes involved in differentiation of keratinocytes
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 250 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, KEGG_LYSOSOME, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, BROWNE_HCMV_INFECTION_16HR_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN

GO Biological Process (4): antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), extracellular matrix disassembly (GO:0022617), obsolete proteolysis involved in protein catabolic process (GO:0051603), proteolysis (GO:0006508)

GO Molecular Function (6): cysteine-type endopeptidase activity (GO:0004197), serine-type endopeptidase activity (GO:0004252), cysteine-type peptidase activity (GO:0008234), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), lysosomal lumen (GO:0043202)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Extracellular matrix organization	2
Adaptive Immune System	2
Immune System	2
Antigen processing-Cross presentation	1
Degradation of the extracellular matrix	1
Toll-like Receptor Cascades	1
Collagen formation	1
Transcriptional regulation by RUNX1	1
Class I MHC mediated antigen processing & presentation	1
Innate Immune System	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endopeptidase activity	2
antigen processing and presentation of exogenous peptide antigen	1
antigen processing and presentation of peptide antigen via MHC class II	1
cellular component disassembly	1
extracellular matrix organization	1
protein metabolic process	1
cysteine-type peptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cellular anatomical structure	1
lytic vacuole	1
lysosome	1
vacuolar lumen	1

Protein interactions and networks

STRING

1209 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTSV	TIMP1	P01033	704
CTSV	SCUBE2	Q9NQ36	697
CTSV	ZNF157	P51786	671
CTSV	TIMP3	P35625	600
CTSV	MYBL2	P10244	584
CTSV	GRB7	Q14451	582
CTSV	LGMN	Q99538	573
CTSV	ARAF	P07557	555
CTSV	MMP11	P24347	554
CTSV	ZNF41	P51814	553
CTSV	BAG1	Q99933	540
CTSV	CTSD	P07339	500
CTSV	CSTA	P01040	496
CTSV	CD99	P14209	493
CTSV	GSTM1	P09488	477

IntAct

135 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
CTSV	CTSL	psi-mi:“MI:0915”(physical association)	0.720
CTSV	CTSL	psi-mi:“MI:0914”(association)	0.720
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
ZSCAN12	A2ML1	psi-mi:“MI:0914”(association)	0.530
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
DNAAF19	KLK10	psi-mi:“MI:0914”(association)	0.530
KIR3DS1	PPL	psi-mi:“MI:0914”(association)	0.530
CST1	CTSV	psi-mi:“MI:0914”(association)	0.530
CTSK	CTSV	psi-mi:“MI:0914”(association)	0.530
MMRN1	CTSV	psi-mi:“MI:0914”(association)	0.530
DTL	DNAJA2	psi-mi:“MI:0914”(association)	0.530
CST6	CTSV	psi-mi:“MI:0914”(association)	0.530
KNG1	CTSV	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530

BioGRID (127): CTSV (Affinity Capture-MS), CTSL (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS), SSR4 (Co-fractionation), CTSV (Proximity Label-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS), CTSV (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4F2V5, O35186, O45734, O60911, O65039, O65493, O70370, O97397, P04988, P06797, P07154, P07711, P12412, P13277, P25251, P25326, P25773, P25774, P25782, P25784, P25803, P25975, P43156, P43235, P43236, P54640, P55097, P61276, P61277, Q02765, Q23894, Q24940, Q26636, Q28944, Q3ZKN1, Q5E968, Q5E998, Q63088, Q86GF7, Q8H166

Diamond homologs: A0A068CNX1, A0A072UTP9, A0A0F7G352, A0A1S4F2V5, A2XQE8, A5HII1, B2LSD2, F4JNL3, O35186, O45734, O46427, O60911, O65039, O65493, O70370, O97397, P00785, P00786, P04989, P05167, P06797, P07154, P07711, P09648, P09668, P0DO76, P12412, P13277, P15242, P25251, P25326, P25773, P25774, P25776, P25777, P25778, P25782, P25784, P25803, P25804

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1189 predictions. Top by Δscore:

Variant	Effect	Δscore
9:97034721:TATA:T	donor_loss	1.0000
9:97034723:TA:T	donor_loss	1.0000
9:97034724:ACC:A	donor_loss	1.0000
9:97034725:CCTG:C	donor_loss	1.0000
9:97034749:G:A	donor_gain	1.0000
9:97034839:AATGC:A	acceptor_gain	1.0000
9:97034841:TGC:T	acceptor_gain	1.0000
9:97034844:C:CC	acceptor_gain	1.0000
9:97035523:CTTA:C	donor_loss	1.0000
9:97035524:TTACC:T	donor_loss	1.0000
9:97035525:TACCT:T	donor_loss	1.0000
9:97035526:A:AC	donor_gain	1.0000
9:97035526:AC:A	donor_gain	1.0000
9:97035526:ACCT:A	donor_loss	1.0000
9:97035527:C:CA	donor_gain	1.0000
9:97035527:CC:C	donor_gain	1.0000
9:97035527:CCT:C	donor_gain	1.0000
9:97035527:CCTG:C	donor_gain	1.0000
9:97035527:CCTGA:C	donor_gain	1.0000
9:97035633:CCA:C	acceptor_gain	1.0000
9:97035634:CA:C	acceptor_gain	1.0000
9:97035634:CAC:C	acceptor_gain	1.0000
9:97035636:C:CC	acceptor_gain	1.0000
9:97036479:T:A	donor_gain	1.0000
9:97036522:CCA:C	donor_gain	1.0000
9:97036526:TGC:T	donor_gain	1.0000
9:97036545:T:TA	donor_gain	1.0000
9:97037246:TCTCA:T	donor_loss	1.0000
9:97037247:CTCAC:C	donor_loss	1.0000
9:97037248:TCA:T	donor_loss	1.0000

AlphaMissense

2229 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:97036721:A:C	F141L	0.996
9:97036721:A:T	F141L	0.996
9:97036723:A:G	F141L	0.996
9:97036658:G:C	S162R	0.994
9:97036658:G:T	S162R	0.994
9:97036660:T:G	S162R	0.994
9:97034731:T:A	K300N	0.993
9:97034731:T:G	K300N	0.993
9:97036718:A:C	S142R	0.993
9:97036718:A:T	S142R	0.993
9:97036720:T:G	S142R	0.993
9:97037523:G:C	F73L	0.993
9:97037523:G:T	F73L	0.993
9:97037525:A:G	F73L	0.993
9:97032986:C:G	C323S	0.992
9:97032987:A:T	C323S	0.992
9:97033033:C:A	W307C	0.992
9:97033033:C:G	W307C	0.992
9:97034728:G:C	N301K	0.992
9:97034728:G:T	N301K	0.992
9:97036659:C:A	S162I	0.991
9:97036729:A:G	W139R	0.991
9:97036729:A:T	W139R	0.991
9:97034742:A:G	W297R	0.990
9:97034742:A:T	W297R	0.990
9:97036727:C:A	W139C	0.990
9:97036727:C:G	W139C	0.990
9:97033035:A:G	W307R	0.989
9:97033035:A:T	W307R	0.989
9:97034732:T:A	K300I	0.989

dbSNP variants (sampled 300 via entrez): RS1000097893 (9:97038872 G>A), RS1000293830 (9:97029404 G>A), RS1000372192 (9:97041575 A>C,G), RS1000530718 (9:97034238 T>C), RS1000698763 (9:97039765 C>G,T), RS1000762951 (9:97041254 T>A), RS1000921605 (9:97038121 G>C,T), RS1001034259 (9:97038461 C>A,G), RS1001180847 (9:97036910 G>A,C), RS1001213313 (9:97039677 G>C), RS1001252311 (9:97030741 T>C), RS1001421311 (9:97036616 C>A,T), RS1001718262 (9:97039951 A>T), RS1002271885 (9:97032571 C>T), RS1002619735 (9:97038792 G>A,C)

Disease associations

OMIM: gene MIM:603308 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111361 (SELECTIVITY GROUP), CHEMBL3272 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,242 (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
CHEMBL218394	BOCEPREVIR	4	2,760
CHEMBL231813	TELAPREVIR	4	3,301
CHEMBL4802135	NIRMATRELVIR	4	1,262
CHEMBL481611	ODANACATIB	3	804
CHEMBL203665	RELACATIB	2	115

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — C1: Papain

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

Ligand	Action	Affinity	Parameter
VBY-825	Inhibition	9.6	pKi
citibrasine	Inhibition	6.7	pKi
petesicatib	Inhibition	6.15	pIC50
Citrusinine II	Inhibition	5.38	pKi

Binding affinities (BindingDB)

22 measured of 66 human assays (66 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-2-(1-benzofuran-2-ylformamido)-4-methyl-N-[(4S,7R)-7-methyl-3-oxo-1-(pyridine-2-sulfonyl)azepan-4-yl]pentanamide	KI	13 nM
N-[(1S)-2-[(3aS,6S,6aS)-6-chloro-3-oxo-3a,5,6,6a-tetrahydrofuro[3,2-b]pyrrol-4-yl]-1-cyclohexyl-2-oxoethyl]-3-imidazol-1-ylbenzamide	KI	440 nM	US-8552202: Furo[3, 2-B] pyrrol-3-ones as cathespin S inhibitors
(2S)-2-(1-benzofuran-2-ylformamido)-4-methyl-N-[(4S)-3-oxo-1-(pyridine-2-sulfonyl)azepan-4-yl]pentanamide	KI	500 nM
N-[(1S)-2-[(3aS,6S,6aS)-6-chloro-3-oxo-3a,5,6,6a-tetrahydrofuro[3,2-b]pyrrol-4-yl]-1-cyclohexyl-2-oxoethyl]-3-(tetrazol-1-yl)benzamide	KI	650 nM	US-8552202: Furo[3, 2-B] pyrrol-3-ones as cathespin S inhibitors
N-[(1S)-2-[(3aS,6S,6aS)-6-chloro-3-oxo-3a,5,6,6a-tetrahydrofuro[3,2-b]pyrrol-4-yl]-1-cyclohexyl-2-oxoethyl]benzamide	KI	780 nM	US-8552202: Furo[3, 2-B] pyrrol-3-ones as cathespin S inhibitors
Dipeptidyl nitrile inhibitor, 22	IC50	2000 nM
Dipeptidyl nitrile inhibitor, 7	IC50	2510 nM
6-methoxy-2-(4-methoxyphenyl)-1-benzopyran-4-one	EC50	3920 nM
Dipeptidyl nitrile inhibitor, 10	IC50	3980 nM
Dipeptidyl nitrile inhibitor, 26	IC50	3980 nM
N-[(1S)-2-[(3aS,6S,6aS)-6-chloro-3-oxo-3a,5,6,6a-tetrahydrofuro[3,2-b]pyrrol-4-yl]-1-(4-methylcyclohexyl)-2-oxoethyl]-3-imidazol-1-ylbenzamide	KI	4000 nM	US-8552202: Furo[3, 2-B] pyrrol-3-ones as cathespin S inhibitors
N-[(1S)-2-[(3aS,6R,6aS)-6-chloro-3-oxo-3a,5,6,6a-tetrahydrofuro[3,2-b]pyrrol-4-yl]-1-cyclohexyl-2-oxoethyl]-3-imidazol-1-ylbenzamide	KI	5000 nM	US-8552202: Furo[3, 2-B] pyrrol-3-ones as cathespin S inhibitors
Dipeptidyl nitrile inhibitor, 1	IC50	5010 nM
Dipeptidyl nitrile inhibitor, 8	IC50	5010 nM
Dipeptidyl nitrile inhibitor, 11	IC50	5010 nM
Dipeptidyl nitrile inhibitor, 24	IC50	5010 nM
N-[(1S)-2-[(3aS,6S,6aS)-6-fluoro-3-oxo-3a,5,6,6a-tetrahydrofuro[3,2-b]pyrrol-4-yl]-1-cyclohexyl-2-oxoethyl]-3-(tetrazol-1-yl)benzamide	KI	6000 nM	US-8552202: Furo[3, 2-B] pyrrol-3-ones as cathespin S inhibitors
Dipeptidyl nitrile inhibitor, 25	IC50	6310 nM
Dipeptidyl nitrile inhibitor, 13	IC50	7940 nM
Dipeptidyl nitrile inhibitor, 23	IC50	7940 nM
Dipeptidyl nitrile inhibitor, 14	IC50	10000 nM
Dipeptidyl nitrile inhibitor, 21	IC50	10000 nM

ChEMBL bioactivities

153 potent at pChembl≥5 of 169 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.20	Ki	0.063	nM	RELACATIB
8.74	Ki	1.8	nM	CHEMBL286364
8.70	IC50	1.995	nM	CHEMBL554065
8.65	Ki	2.25	nM	CHEMBL6173867
8.50	IC50	3.162	nM	CHEMBL562844
8.20	IC50	6.31	nM	CHEMBL549378
8.20	IC50	6.31	nM	CHEMBL550872
8.10	IC50	7.943	nM	CHEMBL549791
7.78	IC50	16.6	nM	CHEMBL1289645
7.70	IC50	19.95	nM	CHEMBL562915
7.60	IC50	25.12	nM	CHEMBL559880
7.55	IC50	28	nM	CHEMBL1288530
7.54	IC50	29	nM	CHEMBL194068
7.53	IC50	29.5	nM	CHEMBL1289305
7.44	IC50	36.3	nM	CHEMBL1289644
7.40	IC50	39.81	nM	CHEMBL557455
7.20	IC50	63.1	nM	CHEMBL556436
7.16	IC50	69	nM	CHEMBL1288532
7.12	IC50	75	nM	BOCEPREVIR
7.10	IC50	79	nM	CHEMBL196896
7.10	IC50	79	nM	CHEMBL1288531
7.00	Ki	100	nM	CHEMBL3648398
7.00	IC50	100	nM	CHEMBL555122
6.89	IC50	130	nM	CHEMBL191584
6.88	IC50	131	nM	CHEMBL390474
6.85	IC50	140	nM	GALLINAMIDE A
6.80	IC50	158	nM	CHEMBL230474
6.80	IC50	158.5	nM	CHEMBL563471
6.80	IC50	158.5	nM	CHEMBL564626
6.77	IC50	170	nM	CHEMBL234367
6.77	Ki	170	nM	CHEMBL3648411
6.75	IC50	180	nM	CHEMBL193582
6.74	IC50	182	nM	CHEMBL568171
6.72	IC50	190	nM	CHEMBL196298
6.70	IC50	200	nM	CHEMBL5430978
6.70	IC50	199.5	nM	CHEMBL551805
6.70	IC50	199.5	nM	CHEMBL559238
6.70	IC50	199.5	nM	CHEMBL564131
6.70	Ki	200	nM	CITIBRASINE
6.62	Ki	240	nM	CHEMBL3648405
6.62	IC50	239.9	nM	CHEMBL567341
6.60	IC50	251.2	nM	CHEMBL551060
6.54	IC50	290	nM	CHEMBL196240
6.47	IC50	340	nM	CHEMBL195963
6.41	IC50	390	nM	CHEMBL197509
6.40	Ki	400	nM	CHEMBL2042470
6.40	IC50	398.1	nM	CHEMBL561725
6.40	IC50	398.1	nM	CHEMBL565079
6.38	IC50	420	nM	CHEMBL4438688
6.37	IC50	430	nM	CHEMBL190053

PubChem BioAssay actives

169 with measured affinity, of 299 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
N-[(2S)-4-methyl-1-[[(4S,7R)-7-methyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide	1797898: Enzyme Inhibition Assay from Article 10.1021/jm050915u: “Structure activity relationships of 5-, 6-, and 7-methyl-substituted azepan-3-one cathepsin K inhibitors.”	ki	0.0001	uM
N-[(2S)-4-methyl-1-oxo-1-[[(4S)-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl]amino]pentan-2-yl]-1-benzofuran-2-carboxamide	1797898: Enzyme Inhibition Assay from Article 10.1021/jm050915u: “Structure activity relationships of 5-, 6-, and 7-methyl-substituted azepan-3-one cathepsin K inhibitors.”	ki	0.0018	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-3-[3-[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0020	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-3-[3-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0032	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-1-oxo-3-[3-(1,3,4-thiadiazol-2-yl)phenyl]propan-2-yl]-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0063	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-3-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0063	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-3-[3-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0079	uM
2-chloro-N-[1-[(1-methylpyrazol-3-yl)amino]-1,2-dioxopentan-3-yl]-4-(pyridin-2-ylmethoxy)-3-(trifluoromethyl)benzamide	539534: Inhibition of human cathepsin V by fluorescence assay	ic50	0.0166	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-3-[3-(1,3,4-oxadiazol-2-yl)phenyl]-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0199	uM
N-[(2S)-1-(cyanomethylamino)-1-oxo-3-[3-(1,3,4-thiadiazol-2-yl)phenyl]propan-2-yl]benzamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0251	uM
(2S)-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-3-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]butanamide	538816: Inhibition of human Cat V	ic50	0.0280	uM
[(3S)-4,4-dimethyl-2-oxopyrrolidin-3-yl] N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate	242468: Inhibitory concentration against human cathepsin V by fluorescence assay using 2 uM Cbz-Phe-Arg-AMC	ic50	0.0290	uM
2-chloro-N-[1,2-dioxo-1-(1H-pyrazol-5-ylamino)pentan-3-yl]-3-(trifluoromethyl)benzamide	539534: Inhibition of human cathepsin V by fluorescence assay	ic50	0.0295	uM
2-chloro-N-[4-[(1-methylpyrazol-3-yl)amino]-3,4-dioxobutan-2-yl]-4-(pyridin-2-ylmethoxy)-3-(trifluoromethyl)benzamide	539534: Inhibition of human cathepsin V by fluorescence assay	ic50	0.0363	uM
N-[(2S)-3-[3-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]phenyl]-1-(cyanomethylamino)-1-oxopropan-2-yl]-3-tert-butyl-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0398	uM
N-[(2S)-1-(cyanomethylamino)-1-oxo-3-(3-pyridazin-3-ylphenyl)propan-2-yl]benzamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.0631	uM
(2S)-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-2-[[(1S)-1-[4-[4-[(1R)-2,2-difluoro-1-hydroxyethyl]phenyl]phenyl]-2,2,2-trifluoroethyl]amino]-3-methylbutanamide	538816: Inhibition of human Cat V	ic50	0.0690	uM
(1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-[(2S)-2-(tert-butylcarbamoylamino)-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide	508158: Inhibition of human Cathepsin V	ic50	0.0750	uM
[(3S)-4,4-dimethyl-2-oxooxolan-3-yl] N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate	242468: Inhibitory concentration against human cathepsin V by fluorescence assay using 2 uM Cbz-Phe-Arg-AMC	ic50	0.0790	uM
1-[4-[4-[(1S)-1-[[(2S)-1-[[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-2,2,2-trifluoroethyl]phenyl]phenyl]cyclopropane-1-carboxamide	538816: Inhibition of human Cat V	ic50	0.0790	uM
N-[(2S)-3-[3-[5-(2-aminoethyl)-1,3,4-oxadiazol-2-yl]phenyl]-1-(cyanomethylamino)-1-oxopropan-2-yl]-3-tert-butyl-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.1000	uM
[(2S)-3,3-dimethyl-1-[4-[4-(trifluoromethyl)phenyl]imidazol-1-yl]butan-2-yl] N-[(3S)-1,2-dioxo-1-(1H-pyrazol-5-ylamino)heptan-3-yl]carbamate	242446: Inhibition of 2 lM Cbz-Phe-Arg-AMC binding to human cathepsin V activity in fluorescence assay with 100 mM NaOAc	ic50	0.1300	uM
(4S,5R)-4-(2,3-dimethylphenoxy)-6-oxa-1-azabicyclo[3.2.1]octan-7-one	290159: Inhibition of human recombinant cathepsin V	ic50	0.1310	uM
[(2S)-1-[[(2S)-1-[[(E,2S)-5-[(2S)-3-methoxy-2-methyl-5-oxo-2H-pyrrol-1-yl]-5-oxopent-3-en-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl] (2S,3S)-2-(dimethylamino)-3-methylpentanoate	1063745: Inhibition of human Cathepsin V using Z-Phe-Arg-aminomethylcoumarin as substrate preincubated for 30 mins followed by substrate addition	ic50	0.1400	uM
(4S,5R)-4-phenoxy-6-oxa-1-azabicyclo[3.2.1]octan-7-one	290159: Inhibition of human recombinant cathepsin V	ic50	0.1580	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-3-[3-(1-methylpyrazol-4-yl)phenyl]-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.1585	uM
N-[(2S)-1-(cyanomethylamino)-3-[3-(1,3,4-oxadiazol-2-yl)phenyl]-1-oxopropan-2-yl]benzamide	430242: Inhibition of cathepsin L2 assessed as inhibition of fluorogenic substrate cleavage	ic50	0.1585	uM
[(2S)-3,3-dimethyl-1-[3-[4-(trifluoromethyl)phenyl]pyrazol-1-yl]butan-2-yl] N-[(3S)-1,2-dioxo-1-(1H-pyrazol-5-ylamino)heptan-3-yl]carbamate	242446: Inhibition of 2 lM Cbz-Phe-Arg-AMC binding to human cathepsin V activity in fluorescence assay with 100 mM NaOAc	ic50	0.1700	uM
(1,3,3-trimethyl-2-bicyclo[2.2.1]heptanyl) N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate	242468: Inhibitory concentration against human cathepsin V by fluorescence assay using 2 uM Cbz-Phe-Arg-AMC	ic50	0.1800	uM
4-(cyclopentylamino)-6-(3,5-difluoroanilino)-1,3,5-triazine-2-carbonitrile	444709: Inhibition of human Cathepsin V	ic50	0.1820	uM
2-bicyclo[2.2.1]heptanyl N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate	242468: Inhibitory concentration against human cathepsin V by fluorescence assay using 2 uM Cbz-Phe-Arg-AMC	ic50	0.1900	uM
3-chloro-N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]benzamide	428164: Inhibition of cathepsin L2	ic50	0.1995	uM
N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]-3,5-dimethylbenzamide	428164: Inhibition of cathepsin L2	ic50	0.1995	uM
3-tert-butyl-N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	428164: Inhibition of cathepsin L2	ic50	0.1995	uM
(6S)-5-[(2R)-2-hydroxy-4-methylpentanoyl]-N-[(2S)-3-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]-4-(trifluoromethoxy)butan-2-yl]-5-azaspiro[2.4]heptane-6-carboxamide	1984493: Inhibition of human Cathepsin L2	ic50	0.2000	uM
1,5-dihydroxy-2,3,4-trimethoxy-10-methylacridin-9-one	568361: Inhibition of human recombinant cathepsin V expressed in Pichia pastoris by Lineweaver-Burk double-reciprocal plots	ki	0.2000	uM
6-(3,5-difluoroanilino)-9-ethylpurine-2-carbonitrile	444709: Inhibition of human Cathepsin V	ic50	0.2399	uM
N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]-2,4-dimethyl-1,3-thiazole-5-carboxamide	1799190: Cathepsin Inhibition Assay from Article 10.1016/j.bmcl.2009.05.071: “Dipeptidyl nitrile inhibitors of Cathepsin L.”	ic50	0.2510	uM
[(1S)-2,3-dihydro-1H-inden-1-yl] N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate	242468: Inhibitory concentration against human cathepsin V by fluorescence assay using 2 uM Cbz-Phe-Arg-AMC	ic50	0.2900	uM
[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl] N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate	242468: Inhibitory concentration against human cathepsin V by fluorescence assay using 2 uM Cbz-Phe-Arg-AMC	ic50	0.3400	uM
2-adamantyl N-[(3S)-1,2-dioxo-1-[[(1R)-1-phenylethyl]amino]heptan-3-yl]carbamate	242468: Inhibitory concentration against human cathepsin V by fluorescence assay using 2 uM Cbz-Phe-Arg-AMC	ic50	0.3900	uM
N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]cyclohexene-1-carboxamide	1799190: Cathepsin Inhibition Assay from Article 10.1016/j.bmcl.2009.05.071: “Dipeptidyl nitrile inhibitors of Cathepsin L.”	ic50	0.3980	uM
3-tert-butyl-N-[(2S)-1-(cyanomethylamino)-3-(3-methylphenyl)-1-oxopropan-2-yl]-1-methylpyrazole-5-carboxamide	1799190: Cathepsin Inhibition Assay from Article 10.1016/j.bmcl.2009.05.071: “Dipeptidyl nitrile inhibitors of Cathepsin L.”	ic50	0.3980	uM
2-nitro-7-phenylmethoxy-10H-acridin-9-one	668142: Competitive inhibition of human recombinant cathepsin V expressed in Pichia pastoris using Z-Phe-Arg-MCA as substrate by Lineweaver-Burk plot analysis	ki	0.4000	uM
(2,4-dihydroxyphenyl)-[(1R,2S,3S,4S)-3,4,6,7-tetrahydroxy-3-(4-hydroxybenzoyl)-1-(4-hydroxyphenyl)-2,4-dihydro-1H-naphthalen-2-yl]methanone	1578085: Inhibition of recombinant human cathepsin V using Z-Phe-Arg-7-amido-4-methylcoumarin as substrate by fluorescence assay	ic50	0.4200	uM
[(2S)-3,3-dimethyl-1-[4-[4-(trifluoromethyl)phenyl]pyrazol-1-yl]butan-2-yl] N-[(3S)-1,2-dioxo-1-(1H-pyrazol-5-ylamino)heptan-3-yl]carbamate	242446: Inhibition of 2 lM Cbz-Phe-Arg-AMC binding to human cathepsin V activity in fluorescence assay with 100 mM NaOAc	ic50	0.4300	uM
1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9-one	568361: Inhibition of human recombinant cathepsin V expressed in Pichia pastoris by Lineweaver-Burk double-reciprocal plots	ki	0.5000	uM
N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]-2,5-dimethylthiophene-3-carboxamide	1799190: Cathepsin Inhibition Assay from Article 10.1016/j.bmcl.2009.05.071: “Dipeptidyl nitrile inhibitors of Cathepsin L.”	ic50	0.5010	uM
N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]-3-ethyl-1-methylpyrazole-5-carboxamide	1799190: Cathepsin Inhibition Assay from Article 10.1016/j.bmcl.2009.05.071: “Dipeptidyl nitrile inhibitors of Cathepsin L.”	ic50	0.5010	uM
N-[(2S)-3-(3-chlorophenyl)-1-(cyanomethylamino)-1-oxopropan-2-yl]-1-methyl-3-propan-2-ylpyrazole-5-carboxamide	1799190: Cathepsin Inhibition Assay from Article 10.1016/j.bmcl.2009.05.071: “Dipeptidyl nitrile inhibitors of Cathepsin L.”	ic50	0.5010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	9
trichostatin A	affects cotreatment, increases expression, affects expression	4
sodium arsenite	affects expression, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
beryllium sulfate	increases expression	1
cupric oxide	increases expression	1
benazol P	affects expression	1
1-aminomethylphosphonic acid	increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases 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	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression, affects methylation	1
Sunitinib	decreases expression	1

ChEMBL screening assays

49 unique, capped per target: 49 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5106300	Binding	Selectivity ratio of IC50 for Cathepsin V (unknown origin) to IC50 for Cathepsin K (unknown origin)	Lead optimization of cathepsin K inhibitors for the treatment of Osteoarthritis. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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