CTSB

Summary

CTSB (cathepsin B, HGNC:2527) is a protein-coding gene on chromosome 8p23.1, encoding Cathepsin B (P07858). Thiol protease which is believed to participate in intracellular degradation and turnover of proteins.

This gene encodes a member of the C1 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 multiple protein products. These products include the cathepsin B light and heavy chains, which can dimerize to form the double chain form of the enzyme. This enzyme is a lysosomal cysteine protease with both endopeptidase and exopeptidase activity that may play a role in protein turnover. It is also known as amyloid precursor protein secretase and is involved in the proteolytic processing of amyloid precursor protein (APP). Incomplete proteolytic processing of APP has been suggested to be a causative factor in Alzheimer’s disease, the most common cause of dementia. Overexpression of the encoded protein has been associated with esophageal adenocarcinoma and other tumors. Both Cathepsin B and Cathepsin L are involved in the cleavage of the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon its entry to the human host cell. Multiple pseudogenes of this gene have been identified.

Source: NCBI Gene 1508 — RefSeq curated summary.

At a glance

• Gene–disease (curated): keratolytic winter erythema (Strong, GenCC)
• GWAS associations: 29
• Clinical variants (ClinVar): 203 total — 1 pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001908

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2527
Approved symbol	CTSB
Name	cathepsin B
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164733
Ensembl biotype	protein_coding
OMIM	116810
Entrez	1508

Gene structure

Transcript identifiers

Ensembl transcripts: 199 — 189 protein_coding, 6 retained_intron, 4 nonsense_mediated_decay

ENST00000345125, ENST00000353047, ENST00000420692, ENST00000453527, ENST00000505496, ENST00000524500, ENST00000525076, ENST00000525315, ENST00000526195, ENST00000526645, ENST00000527215, ENST00000527243, ENST00000528965, ENST00000530290, ENST00000530296, ENST00000530640, ENST00000531089, ENST00000531502, ENST00000531551, ENST00000532392, ENST00000532409, ENST00000532656, ENST00000533455, ENST00000533572, ENST00000534149, ENST00000534382, ENST00000534510, ENST00000534636, ENST00000676502, ENST00000676691, ENST00000676755, ENST00000676825, ENST00000676843, ENST00000676952, ENST00000677047, ENST00000677082, ENST00000677283, ENST00000677366, ENST00000677415, ENST00000677418, ENST00000677544, ENST00000677650, ENST00000677671, ENST00000677819, ENST00000677865, ENST00000677873, ENST00000678067, ENST00000678092, ENST00000678145, ENST00000678242, ENST00000678357, ENST00000678598, ENST00000678615, ENST00000678629, ENST00000678929, ENST00000679051, ENST00000679121, ENST00000679128, ENST00000679140, ENST00000679214, ENST00000900653, ENST00000900654, ENST00000900655, ENST00000900656, ENST00000900657, ENST00000900658, ENST00000900659, ENST00000900660, ENST00000900661, ENST00000900662, ENST00000900663, ENST00000900664, ENST00000900665, ENST00000900666, ENST00000900667, ENST00000900668, ENST00000900669, ENST00000900670, ENST00000900671, ENST00000900672, ENST00000900673, ENST00000900674, ENST00000900675, ENST00000900676, ENST00000900677, ENST00000900678, ENST00000900679, ENST00000900680, ENST00000900681, ENST00000900682, ENST00000900683, ENST00000900684, ENST00000900685, ENST00000900686, ENST00000900687, ENST00000900688, ENST00000900689, ENST00000900690, ENST00000900691, ENST00000900692, ENST00000900693, ENST00000900694, ENST00000900695, ENST00000939174, ENST00000939175, ENST00000947600, ENST00000947601, ENST00000947602, ENST00000947603, ENST00000947604, ENST00000947605, ENST00000947606, ENST00000947607, ENST00000947608, ENST00000947609, ENST00000947610, ENST00000947611, ENST00000947612, ENST00000947613, ENST00000947614, ENST00000947615, ENST00000947616, ENST00000947617, ENST00000947618, ENST00000947619, ENST00000947620, ENST00000947621, ENST00000947622, ENST00000947623, ENST00000947624, ENST00000947625, ENST00000947626, ENST00000947627, ENST00000947628, ENST00000947629, ENST00000947630, ENST00000947631, ENST00000947632, ENST00000947633, ENST00000947634, ENST00000947635, ENST00000947636, ENST00000947637, ENST00000947638, ENST00000947639, ENST00000947640, ENST00000947641, ENST00000947642, ENST00000947643, ENST00000947644, ENST00000947645, ENST00000947646, ENST00000947647, ENST00000947648, ENST00000947649, ENST00000947650, ENST00000947651, ENST00000947652, ENST00000947653, ENST00000947654, ENST00000947655, ENST00000947656, ENST00000947657, ENST00000947658, ENST00000947659, ENST00000947660, ENST00000947661, ENST00000947662, ENST00000947663, ENST00000947664, ENST00000947665, ENST00000947666, ENST00000947667, ENST00000947668, ENST00000947669, ENST00000947670, ENST00000947671, ENST00000947672, ENST00000947673, ENST00000947674, ENST00000947675, ENST00000947676, ENST00000947677, ENST00000947678, ENST00000947679, ENST00000947680, ENST00000947681, ENST00000947682, ENST00000947683, ENST00000947684, ENST00000947685, ENST00000947686, ENST00000947687, ENST00000947688, ENST00000947689, ENST00000947690, ENST00000947691, ENST00000947692, ENST00000947693

RefSeq mRNA: 13 — MANE Select: NM_001908 NM_001317237, NM_001384714, NM_001384723, NM_001384724, NM_001384725, NM_001384726, NM_001384727, NM_001384728, NM_001908, NM_147780, NM_147781, NM_147782, NM_147783

CCDS: CCDS5986

Canonical transcript exons

ENST00000353047 — 10 exons

Exon	Start	End
ENSE00001374998	11842524	11845222
ENSE00001724322	11868001	11868087
ENSE00003479917	11850866	11850980
ENSE00003482060	11847679	11847822
ENSE00003562494	11853329	11853479
ENSE00003568987	11847052	11847168
ENSE00003673888	11845661	11845789
ENSE00003678239	11848067	11848152
ENSE00003787603	11852610	11852695
ENSE00003790299	11849046	11849164

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 754.5328 / max 15847.2453, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91900	750.1684	1822
91885	2.4299	837
91893	0.7138	315
91886	0.5664	249
91894	0.3946	176
91899	0.2597	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.90	gold quality
right lobe of thyroid gland	UBERON:0001119	99.83	gold quality
left lobe of thyroid gland	UBERON:0001120	99.82	gold quality
vermiform appendix	UBERON:0001154	99.59	gold quality
endocervix	UBERON:0000458	99.56	gold quality
gall bladder	UBERON:0002110	99.55	gold quality
ectocervix	UBERON:0012249	99.52	gold quality
smooth muscle tissue	UBERON:0001135	99.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.48	gold quality
monocyte	CL:0000576	99.41	gold quality
leukocyte	CL:0000738	99.40	gold quality
upper lobe of left lung	UBERON:0008952	99.40	gold quality
right lung	UBERON:0002167	99.39	gold quality
right adrenal gland cortex	UBERON:0035827	99.39	gold quality
minor salivary gland	UBERON:0001830	99.37	gold quality
islet of Langerhans	UBERON:0000006	99.32	gold quality
right adrenal gland	UBERON:0001233	99.31	gold quality
descending thoracic aorta	UBERON:0002345	99.30	gold quality
right atrium auricular region	UBERON:0006631	99.29	gold quality
granulocyte	CL:0000094	99.27	gold quality
left adrenal gland	UBERON:0001234	99.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.27	gold quality
lower esophagus	UBERON:0013473	99.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.24	gold quality
mucosa of stomach	UBERON:0001199	99.22	gold quality
thoracic aorta	UBERON:0001515	99.22	gold quality
right lobe of liver	UBERON:0001114	99.21	gold quality
ascending aorta	UBERON:0001496	99.21	gold quality
body of uterus	UBERON:0009853	99.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.20	gold quality

Single-cell (SCXA)

Detected in 37 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	12994.50
E-GEOD-110499	yes	11137.37
E-MTAB-9435	yes	3798.89
E-MTAB-8530	yes	3224.00
E-HCAD-15	yes	2907.76
E-CURD-126	yes	2737.38
E-MTAB-8207	yes	2320.09
E-HCAD-13	yes	2241.61
E-MTAB-6308	yes	2217.22
E-MTAB-8410	yes	2027.87
E-MTAB-7407	yes	1995.78
E-MTAB-6653	yes	1985.82
E-GEOD-130148	yes	1658.70
E-CURD-122	yes	1280.01
E-HCAD-36	yes	1159.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREB1, ETS1, ETS2, KLF6, MYOD1, NFKB1, NFKB, PPARA, RELA, SP1, SP3, SP4, STAT1, USF1, USF2

miRNA regulators (miRDB)

65 targeting CTSB, 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-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4279	99.19	66.70	2437

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• role of exocytosis in phorbol ester activation of a proteolytic cascade capable of activating latent transforming growth factor beta (PMID:11815600)
• Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis (PMID:11932257)
• Interaction of human breast fibroblasts with collagen I increases total cathepsin B protein levels (PMID:12072442)
• examination of expression of cathepsin B in articular chondrocytes and two lines of immortalized human chondrocytes (PMID:12086583)
• cathepsin B plays a role in controlling cell death and in limiting damage-associated inflammation (PMID:12185082)
• Cathepsin B carboxydipeptidase specificity analysis using internally quenched fluorescent peptides. (PMID:12201820)
• Cathepsin B expression is significantly associated with the stage of ovarian cancer, debulking success and with progesterone receptors, and may have a role in ovarian cancer pathogenesis. (PMID:12437120)
• Intracellular and extracellular cathepsin B facilitate invasion of MCF-10A neoT cells through reconstituted extracellular matrix in vitro. (PMID:12581740)
• production of cathepsins B and H by tumor cells along with concomitant decrease of their inhibitor, cystatin C, in the CSF might contribute in the process of metastasis and spread of the cancer cells in the leptomeningeal tissues (PMID:12589965)
• cathepsin B is involved in the motor neuron degeneration in ALS. (PMID:12677446)
• In normal conditions and in the presence of IL-1beta, cathepsin B is involved in the activation of plasminogen activator in osteoblasts. (PMID:12726991)
• REVIEW: focus on the molecular regulation of cathepsin B and attendant implications for tumor progression and arthritis; the potential of cathepsin B as a therapeutic target (PMID:12887051)
• T-cell apoptosis induced by antithymocyte globulins was associated with the release of active cathepsin B into the cytosol (PMID:12893746)
• The expression of cathepsin B in non-small cell lung cancer should be considered as a significant prognostic parameter. (PMID:12926111)
• Central role for the lysosomal protease cathepsin B in mediating cell death in lung cancer cells. (PMID:14729603)
• No significant difference in serum cathepsin B levels was observed between patients with benign and malignant ovarian disease. (PMID:14984956)
• role for cathepsin B is reported in human papillomavirus-induced apoptotic signalling (PMID:15016552)
• Cathepsin B is released and catalytically active in T lymphocyte cytosol during supraoptimal activation-induced apoptosis of T cells in vitro and may participate in high dose tolerance in vivo. (PMID:15100281)
• endothelial cell-associated cathepsins B and L are not involved in the invasive growth of capillaries from existing blood vessels and the presence of collagen is necessary for MMP2 expression in endothelial cells (PMID:15255544)
• excessive transcription of the cathepsin B message lacking exons 2 and 3 has significant consequences on cell life (PMID:15262981)
• Extensive mass spectrometry of purified proteins separated under denaturing conditions strongly suggests that presenilin N- and C-terminal fragments, nicastrin, Aph-1, and presenilin enhancer-2 are components of the active gamma-secretase complex. (PMID:15274632)
• Mechanical stress (compression and tension forces) causes an increase in secretion of cathepsins B and L in periodontal ligament cells in vitro. (PMID:15512772)
• Cathepsin B is a protease that contributes to the remodelling of the extracellular matrix and thereby promotes keratinocyte migration during wound healing. (PMID:15679122)
• SK1 down-regulation by TNF is dependent on the lysosomal pathway of apoptosis and specifically on cathepsin B, which functions as an SK1 protease in cells (PMID:15710602)
• tumor-stromal interactions in the context of the bone microenvironment can modulate the expression of the cysteine protease cathepsin B (PMID:15799821)
• results suggest that besides the N-terminal signal peptide also other CB domains contain patterns which are responsible for a differentiated targeting of the molecule, e.g. to the mitochondria, to the nucleus, or to vesicles. (PMID:15807897)
• cathepsins B and L have roles in atypical pituitary adenoma (PMID:15816632)
• Plays a role in Ebola virus entry into cells (PMID:15831716)
• protein levels of cathepsins B (p=0.050) and L (p=0.019) were found to be significantly higher in atypical than in benign meningiomas (PMID:15832773)
• The cathepsin B death pathway is cell type-specific and may contribute to inflammatory cytokine-mediated human tissue injury (PMID:16034129)
• Cathepsin B is responsble for the degradation of insulin-like growth factor-I in endosomes. (PMID:16051222)
• Cathepsin B substrate, BID, serves as molecular switch between apotosis and autophagy in camptothecin treated breast cancer cells. (PMID:16077201)
• These results show that, besides multiple regulatory molecules, intracellular cathepsin B also contributes to the neovascularization process and should be considered as a potential therapeutic target. (PMID:16315320)
• results strongly implicate a pivotal role of cell-matrix interactions for the regulation of cathepsin B localization and activity in melanoma cells (PMID:16381007)
• Cathepsin B caused activation of trypsinogen-1 with a trypsin yield of about 30% of that produced by enterokinase. Proelastase and procarboxypeptidase B was not activated by cathepsin B. (PMID:16534247)
• Cathepsin B specifically cleaves off four C-terminally located amino acids of human CCL20 and generates a CCL20(1-66) isoform with full functional activity. (PMID:16709808)
• hSB1 may function as a regulator of cathepsin B-mediated apoptosis. (PMID:16733801)
• These data imply that confluent cells undergo spontaneous cell death mediated by cathepsin B; Lipopolysaccharides may accelerate this caspase-independent cell death through release of mitochondrial contents and reactive oxygen species. (PMID:16894574)
• expression of human cathepsin L (CSTL) through a genomic transgene results in widespread expression of human CTSL in the mouse that is capable of rescuing the lethality found in CTSB/CTSL double-deficient animals (PMID:16913838)
• cathepsin B is not essential for protection of cytotoxic lymphocytes from the toxic effects of their secreted perforin (PMID:16914553)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctsba	ENSDARG00000055120
mus_musculus	Ctsb	ENSMUSG00000021939
rattus_norvegicus	Ctsb	ENSRNOG00000010331
caenorhabditis_elegans		WBGENE00000781
caenorhabditis_elegans		WBGENE00000782
caenorhabditis_elegans		WBGENE00000784
caenorhabditis_elegans		WBGENE00000785
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), CTSV (ENSG00000136943), TINAG (ENSG00000137251), TINAGL1 (ENSG00000142910), CTSK (ENSG00000143387), CTSS (ENSG00000163131), CTSW (ENSG00000172543), CTSF (ENSG00000174080), CTSO (ENSG00000256043)

Protein

Protein identifiers

Cathepsin B — P07858 (reviewed: P07858)

Alternative names: APP secretase, Cathepsin B1

All UniProt accessions (23): P07858, A0A024R374, A0A7I2V2J1, A0A7I2V302, A0A7I2V367, A0A7I2V440, A0A7I2V4S6, A0A7I2V4Z9, A0A7I2V668, A0A7I2YQK9, A0A7P0NGZ6, E9PCB3, E9PHZ5, E9PIS1, E9PKQ7, E9PKX0, E9PL32, E9PLY3, E9PNL5, E9PR00, E9PR21, E9PS78, E9PSG5

UniProt curated annotations — full annotation on UniProt →

Function. Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Cleaves matrix extracellular phosphoglycoprotein MEPE. Involved in the solubilization of cross-linked TG/thyroglobulin in the thyroid follicle lumen. Has also been implicated in tumor invasion and metastasis.

Subunit / interactions. Dimer of a heavy chain and a light chain cross-linked by a disulfide bond. Interacts with SRPX2. Directly interacts with SHKBP1.

Subcellular location. Lysosome. Melanosome. Secreted. Extracellular space. Apical cell membrane.

Tissue specificity. Expressed in the stratum spinosum of the epidermis. Weak expression is detected in the stratum granulosum.

Disease relevance. Keratolytic winter erythema (KWE) [MIM:148370] An autosomal dominant genodermatosis characterized by recurrent episodes of palmoplantar erythema and epidermal peeling presenting seasonal variation. KWE manifests during childhood. Skin lesions may spread to the dorsum of hands and feet and to the interdigital spaces. Lower legs, knees and thighs may also be involved. A less common finding is a slowly migratory, annular erythema that is seen mostly on the extremities. Between flares, the skin can appear unremarkable. Itching can occur, and hyperhidrosis, associated with a pungent odor, is invariably present. Formation of vesicles is rare, whereas keratolysis that causes the formation of dry blisters is regularly seen. Cold weather, moisture, febrile diseases, and physical and mental stress can trigger exacerbations. In severely affected individuals, skin manifestations persist unremittingly. Penetrance of the disease is high, but expressivity is variable, even within the same family. The gene represented in this entry is involved in disease pathogenesis. Tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB result in CTSB abnormal expression with pathological consequences.

Activity regulation. Inhibited by leupeptin.

Similarity. Belongs to the peptidase C1 family.

RefSeq proteins (13): NP_001304166, NP_001371643, NP_001371652, NP_001371653, NP_001371654, NP_001371655, NP_001371656, NP_001371657, NP_001899, NP_680090, NP_680091, NP_680092, NP_680093 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000169	Pept_cys_AS	Active_site
IPR000668	Peptidase_C1A_C	Domain
IPR012599	Propeptide_C1A	Domain
IPR013128	Peptidase_C1A	Family
IPR025660	Pept_his_AS	Active_site
IPR025661	Pept_asp_AS	Active_site
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily

Pfam: PF00112, PF08127

Enzyme classification (BRENDA):

• EC 3.4.22.1 — cathepsin B (BRENDA: 62 organisms, 466 substrates, 788 inhibitors, 226 Km, 55 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
BENZOYL-DL-ARG-BETA-NAPHTHYLAMIDE	0.53–24	12
BENZYLOXYCARBONYL-ARG-ARG-4-METHYLCOUMARYL-7-AMI	0.006–0.467	11
BENZYLOXYCARBONYL-PHE-ARG-4-METHYLCOUMARYL-7-AMI	0.021–0.252	8
BENZYLOXYCARBONYL-VAL-LYS-LYS-ARG-4-METHOXY-BETA	0.012–0.91	6
O-AMINOBENZOYL-L-PHE-L-ARG-L-LYS-EPSILON-N-2,4-D	0.0125–0.047	6
BENZOYL-DL-ARG-P-NITROANILIDE	0.685–20	5
BENZYLOXYCARBONYL-ALA-ARG-ARG-4-METHOXY-BETA-NAP	0.022–1.25	5
BENZOYL-PHE-VAL-ARG-P-NITROANILIDE	0.0232–0.18	4
BENZOYL-PRO-PHE-ARG-P-NITROANILIDE	0.2–1	4
BENZYLOXYCARBONYL-ARG-ARG-7-AMIDO-4-METHYLCOUMAR	0.099–0.85	3
2,4-DINITROPHENYL-GFLFW-OH	0.0005–0.0017	2
4-(4-DIMETHYLAMINOPHENYLAZO)BENZOYL-L-ARG-L-LEU-	0.0028–0.0036	2
4-(4-DIMETHYLAMINOPHENYLAZO)BENZOYL-L-ARG-L-LEU-	0.0035–0.0053	2
4-(4-DIMETHYLAMINOPHENYLAZO)BENZOYL-L-LEU-L-ARG-	0.0046–0.0078	2
4-(4-DIMETHYLAMINOPHENYLAZO)BENZOYL-L-LEU-L-ARG-	0.0037–0.0082	2

UniProt features (57 total): strand 18, helix 13, disulfide bond 6, sequence variant 4, turn 4, chain 3, active site 3, propeptide 2, signal peptide 1, glycosylation site 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
8B4T	X-RAY DIFFRACTION	1.45
9VA8	X-RAY DIFFRACTION	1.5
9XHR	X-RAY DIFFRACTION	1.5
8HE9	X-RAY DIFFRACTION	1.55
8HEI	X-RAY DIFFRACTION	1.55
6AY2	X-RAY DIFFRACTION	1.6
8B5F	X-RAY DIFFRACTION	1.7
3CBJ	X-RAY DIFFRACTION	1.8
5MBL	X-RAY DIFFRACTION	1.81
1GMY	X-RAY DIFFRACTION	1.9
8HEN	X-RAY DIFFRACTION	1.95
1CSB	X-RAY DIFFRACTION	2
1HUC	X-RAY DIFFRACTION	2.1
3AI8	X-RAY DIFFRACTION	2.11
2IPP	X-RAY DIFFRACTION	2.15
3PBH	X-RAY DIFFRACTION	2.5
3K9M	X-RAY DIFFRACTION	2.61
3CBK	X-RAY DIFFRACTION	2.67
5MBM	X-RAY DIFFRACTION	2.76
1PBH	X-RAY DIFFRACTION	3.2
2PBH	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07858-F1	91.95	0.82

Functional residue map

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

Catalytic / active sites (3): 108; 278; 298

Post-translational modifications (1): 220

Disulfide bonds (6): 93–122, 105–150, 141–207, 142–146, 179–211, 187–198

Glycosylation sites (1): 192

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
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-6798695	Neutrophil degranulation
R-HSA-9766229	Degradation of CDH1
R-HSA-9958810	SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)
R-HSA-1280218	Adaptive Immune System
R-HSA-1474228	Degradation of the extracellular matrix
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

MSigDB gene sets: 417 (showing top): MODULE_172, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, MODULE_128, IVANOVA_HEMATOPOIESIS_MATURE_CELL

GO Biological Process (10): proteolysis (GO:0006508), thyroid hormone generation (GO:0006590), collagen catabolic process (GO:0030574), epithelial cell differentiation (GO:0030855), regulation of apoptotic process (GO:0042981), decidualization (GO:0046697), symbiont entry into host cell (GO:0046718), obsolete proteolysis involved in protein catabolic process (GO:0051603), cellular response to thyroid hormone stimulus (GO:0097067), regulation of catalytic activity (GO:0050790)

GO Molecular Function (8): cysteine-type endopeptidase activity (GO:0004197), collagen binding (GO:0005518), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), proteoglycan binding (GO:0043394), endopeptidase activity (GO:0004175), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (14): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), external side of plasma membrane (GO:0009897), apical plasma membrane (GO:0016324), extracellular matrix (GO:0031012), endolysosome lumen (GO:0036021), melanosome (GO:0042470), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), peptidase inhibitor complex (GO:1904090), ficolin-1-rich granule lumen (GO:1904813), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Innate Immune System	2
Immune System	2
Extracellular matrix organization	2
Degradation of the extracellular matrix	1
Toll-like Receptor Cascades	1
Collagen formation	1
Adaptive Immune System	1
Regulation of CDH1 Function	1
Activation of STAT3 by cadherin engagement	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
peptidase activity	2
protein metabolic process	1
thyroid hormone metabolic process	1
catabolic process	1
collagen metabolic process	1
cell differentiation	1
epithelium development	1
apoptotic process	1
regulation of programmed cell death	1
maternal placenta development	1
developmental process involved in reproduction	1
tissue development	1
viral life cycle	1
symbiont entry into host	1
cellular response to hormone stimulus	1
response to thyroid hormone	1
regulation of molecular function	1
endopeptidase activity	1
cysteine-type peptidase activity	1
protein-containing complex binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
protein binding	1
carbohydrate derivative binding	1
binding	1
lytic vacuole	1
plasma membrane	1
cell surface	1
side of membrane	1
apical part of cell	1
plasma membrane region	1
external encapsulating structure	1
endosome lumen	1
endolysosome	1
lysosomal lumen	1
pigment granule	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

4503 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTSB	ANXA2	P07355	952
CTSB	CST3	P01034	950
CTSB	NLRP3	Q96P20	938
CTSB	CTSD	P07339	923
CTSB	APP	P05067	897
CTSB	LGMN	Q99538	871
CTSB	CSTA	P01040	851
CTSB	CSTB	P04080	845
CTSB	CASP1	P29466	814
CTSB	CST4	P01036	783
CTSB	MMP9	P14780	767
CTSB	LAMP1	P11279	766
CTSB	TYRP1	P17643	765
CTSB	TMPRSS2	O15393	763
CTSB	A2M	P01023	758

IntAct

103 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
BRAF	KRAS	psi-mi:“MI:0914”(association)	0.680
IRS4	PIK3R2	psi-mi:“MI:0914”(association)	0.640
MLH1	CTSB	psi-mi:“MI:0915”(physical association)	0.600
CTSB	MLH1	psi-mi:“MI:0915”(physical association)	0.600
MLH1	CTSB	psi-mi:“MI:0403”(colocalization)	0.600
CTSB	AMBP	psi-mi:“MI:0915”(physical association)	0.600
AMBP	CTSB	psi-mi:“MI:0403”(colocalization)	0.600
CTSB	CSTA	psi-mi:“MI:0407”(direct interaction)	0.590
BOD1	CTSB	psi-mi:“MI:0915”(physical association)	0.560
RGS2	CTSB	psi-mi:“MI:0915”(physical association)	0.550
CTSB	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.540
CTSB	ADAMTSL4	psi-mi:“MI:0403”(colocalization)	0.540
gag-pol	EIF3F	psi-mi:“MI:0914”(association)	0.460
Lrp2	CTSB	psi-mi:“MI:0407”(direct interaction)	0.440
S	CTSB	psi-mi:“MI:0570”(protein cleavage)	0.440
SPHK1	CTSB	psi-mi:“MI:0194”(cleavage reaction)	0.440
CTSB	SPHK1	psi-mi:“MI:0194”(cleavage reaction)	0.440

BioGRID (316): CTSB (Affinity Capture-RNA), MSI2 (Co-fractionation), CTSB (Two-hybrid), CTSB (Two-hybrid), CTSB (Proximity Label-MS), CTSB (Proximity Label-MS), CTSB (Proximity Label-MS), CTSB (Proximity Label-MS), CTSB (Proximity Label-MS), CTSB (Affinity Capture-MS), CTSB (Proximity Label-MS), CTSB (Affinity Capture-RNA), CTSB (Affinity Capture-MS), CTSB (Affinity Capture-MS), CTSB (Affinity Capture-MS)

ESM2 similar proteins: A0A072UTP9, A1E295, G5EGP8, O45734, O65039, O70370, P00787, P04988, P05689, P07688, P07711, P07858, P10605, P19092, P25326, P25773, P25774, P25792, P25793, P25802, P25804, P25807, P43157, P43233, P43296, P43507, P43508, P43509, P43510, P83205, P90850, Q02765, Q26534, Q3SZI1, Q4R5M2, Q5E998, Q5R6D1, Q63088, Q6PN98, Q8HY81

Diamond homologs: A0A0F7G352, A0E358, A1E295, F4HVZ1, G5EGP8, O46427, O60911, O97578, P00787, P05167, P05993, P07688, P07711, P07858, P09668, P0DO76, P10605, P19092, P25774, P25778, P25792, P25793, P25802, P25807, P32954, P36400, P43157, P43233, P43507, P43508, P43509, P43510, P49935, P53634, P81494, P83205, P90850, P92131, P92132, P92133

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
aloxistatin	“down-regulates activity”	CTSB	“chemical inhibition”
CTSB	“up-regulates activity”	S	cleavage
CTSB	“down-regulates quantity by destabilization”	BGLAP	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	97
Likely benign	43
Benign	31

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1807804	GRCh37/hg19 8p23.1(chr8:8093066-12548732)x1	Pathogenic

SpliceAI

2220 predictions. Top by Δscore:

Variant	Effect	Δscore
8:11845785:CACTC:C	acceptor_gain	1.0000
8:11845787:CTC:C	acceptor_gain	1.0000
8:11845788:TC:T	acceptor_gain	1.0000
8:11845789:CC:C	acceptor_gain	1.0000
8:11845789:CCTG:C	acceptor_loss	1.0000
8:11845790:C:CC	acceptor_gain	1.0000
8:11845790:CT:C	acceptor_loss	1.0000
8:11847049:CA:C	donor_loss	1.0000
8:11847050:A:AC	donor_gain	1.0000
8:11847050:A:AT	donor_loss	1.0000
8:11847051:C:A	donor_gain	1.0000
8:11847051:C:CT	donor_gain	1.0000
8:11847051:CC:C	donor_loss	1.0000
8:11847051:CCTGA:C	donor_gain	1.0000
8:11847169:C:CC	acceptor_gain	1.0000
8:11847821:CC:C	acceptor_gain	1.0000
8:11847822:CC:C	acceptor_gain	1.0000
8:11848065:A:AC	donor_gain	1.0000
8:11848066:C:CC	donor_gain	1.0000
8:11848066:CCT:C	donor_gain	1.0000
8:11848066:CCTA:C	donor_gain	1.0000
8:11848148:TACAG:T	acceptor_gain	1.0000
8:11848149:ACAG:A	acceptor_gain	1.0000
8:11848150:CAG:C	acceptor_gain	1.0000
8:11848150:CAGC:C	acceptor_gain	1.0000
8:11848152:GCTG:G	acceptor_loss	1.0000
8:11848153:C:CC	acceptor_gain	1.0000
8:11848153:CTG:C	acceptor_loss	1.0000
8:11849040:ACTC:A	donor_loss	1.0000
8:11849042:TCAC:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014976 (8:11847540 G>A,C,T), RS1000089744 (8:11866892 TTGGATTCAAAGAGAG>T), RS1000104175 (8:11862982 C>T), RS1000148485 (8:11856656 G>A,C), RS1000177425 (8:11845721 C>G), RS1000192485 (8:11869387 G>A,C), RS1000246854 (8:11863118 G>A), RS1000261257 (8:11846382 T>C), RS1000333122 (8:11856429 G>A,C), RS1000333869 (8:11860018 G>A,C), RS1000336436 (8:11851113 G>A,C), RS1000471396 (8:11847631 A>G), RS1000700663 (8:11866442 G>A,T), RS1000737292 (8:11843303 T>C), RS1000750938 (8:11866299 C>A,T)

Disease associations

OMIM: gene MIM:116810 | disease phenotypes: MIM:148370

GenCC curated gene-disease

Disease	Classification	Inheritance
keratolytic winter erythema	Strong	Autosomal dominant

Mondo (1): keratolytic winter erythema (MONDO:0007854)

Orphanet (1): Keratolytic winter erythema (Orphanet:50943)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000951	Abnormality of the skin
HP:0000975	Hyperhidrosis
HP:0007410	Palmoplantar hyperhidrosis
HP:0010783	Erythema
HP:0200039	Pustule

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST003681_2	C-reactive protein levels or triglyceride levels (pleiotropy)	2.000000e-10
GCST004009_3	Leprosy	5.000000e-11
GCST004902_24	Parkinson’s disease	6.000000e-12
GCST006613_74	Triglycerides	5.000000e-13
GCST007325_28	General risk tolerance (MTAG)	4.000000e-08
GCST009152_3	Triglyceride levels	2.000000e-23
GCST009267_16	Dental caries (decayed, missing and filled teeth)	4.000000e-06
GCST009325_98	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	4.000000e-16
GCST009373_2	Parkinson’s disease in GBA mutation carriers	6.000000e-06
GCST010002_269	Refractive error	1.000000e-24
GCST010132_11	Processed meat consumption	4.000000e-10
GCST010132_14	Processed meat consumption	2.000000e-15
GCST010132_15	Processed meat consumption	1.000000e-09
GCST010142_4	Fish- and plant-related diet	2.000000e-12
GCST010142_6	Fish- and plant-related diet	3.000000e-12
GCST010142_89	Fish- and plant-related diet	4.000000e-16
GCST010142_90	Fish- and plant-related diet	7.000000e-15
GCST010703_306	Brain morphology (MOSTest)	5.000000e-26
GCST010991_4	Parkinson’s disease	6.000000e-11
GCST011202_7	Dilated cardiomyopathy (MTAG)	5.000000e-09
GCST012226_745	Waist circumference adjusted for body mass index	9.000000e-10
GCST012228_419	Waist-hip index	2.000000e-08
GCST012231_43	A body shape index	4.000000e-08
GCST90002379_115	Basophil count	2.000000e-09
GCST90002380_57	Basophil percentage of white cells	1.000000e-09
GCST90013445_47	Type 1 diabetes	1.000000e-10
GCST90013445_57	Type 1 diabetes	1.000000e-10
GCST90020024_154	A body shape index	3.000000e-08
GCST90020029_976	Waist circumference adjusted for body mass index	1.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004530	triglyceride measurement
EFO:0008579	risk-taking behaviour
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536155	Keratolytic winter erythema (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111396 (SELECTIVITY GROUP), CHEMBL4072 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 63,738 (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
CHEMBL1454910	NITROXOLINE	4	1,860
CHEMBL218394	BOCEPREVIR	4	2,760
CHEMBL231813	TELAPREVIR	4	3,301
CHEMBL451887	CARFILZOMIB	4	12,508
CHEMBL1241348	FALDAPREVIR	3	397
CHEMBL481611	ODANACATIB	3	804
CHEMBL203665	RELACATIB	2	115
CHEMBL296588	PEPSTATIN	2	26,094
CHEMBL359965	ALLICIN	2	14,806
CHEMBL371064	BALICATIB	2	97
CHEMBL5095230	ATUZAGINSTAT	2	72
CHEMBL63440	ALOXISTATIN	2	723
CHEMBL91704	K-777	2	201

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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
Z-Arg-Leu-Val-Agly-Ile-Val-OMe	Inhibition	10.1	pKi
VBY-825	Inhibition	9.48	pKi
compound 1 [PMID: 40415551]	Inhibition	6.36	pIC50
LHVS	Inhibition	5.87	pIC50
K11777	Inhibition	5.52	pKi

Binding affinities (BindingDB)

258 measured of 437 human assays (441 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S,3S)-3-[[(1S)-1-(isoamylcarbamoyl)-3-methyl-butyl]carbamoyl]oxirane-2-carboxylic acid	IC50	1.53 nM
Mercaptomethyl ketone Inhibitor, 53	KI	2 nM
Mercaptomethyl ketone Inhibitor, 52	KI	4.7 nM
(3S)-3-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]-5-(2,6-dimethylbenzoyl)oxy-4-oxopentanoic acid	IC50	11.5 nM	US-9345789: Specific inhibitors and active site probes for legumain
(2R,3R)-3-[[(1S)-1-(4-guanidinobutylcarbamoyl)-3-methyl-butyl]carbamoyl]oxirane-2-carboxylic acid	IC50	12.3 nM
(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
(2S)-3,3-dimethyl-1-[3-(pyridin-4-yl)-1H-pyrazol-1-yl]butan-2-yl N-[(3S)-2-oxo-1-(pyridine-2-sulfonamido)heptan-3-yl]carbamate	IC50	13 nM
Mercaptomethyl ketone Inhibitor, 45	KI	13 nM
N-{1-[(cyanomethyl)carbamoyl]cyclohexyl}-4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzamide	EC50	17 nM
(2S)-3,3-dimethyl-1-{3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}butan-2-yl N-[(2S)-1-oxo-1-(1H-pyrazol-5-ylcarbamoyl)hexan-2-yl]carbamate	IC50	20 nM
(2S,4R)-N-[(3S)-1-(butylamino)-1,2-dioxohexan-3-yl]-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonylpyrrolidine-2-carboxamide	IC50	29.4 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1,2-dioxo-1-(2-phenylethylamino)pentan-3-yl]pyrrolidine-2-carboxamide	IC50	30.2 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-N-[(3S)-1-(benzylamino)-1,2-dioxohexan-3-yl]-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonylpyrrolidine-2-carboxamide	IC50	31 nM	US-8729061: Pyrrolidine derivatives
(2S)-2-(1-benzofuran-2-ylformamido)-4-methyl-N-[(4S,5S)-5-methyl-3-oxo-1-(pyridine-2-sulfonyl)azepan-4-yl]pentanamide	KI	32 nM
(2S)-1-(5,6-dichloro-1H-1,3-benzodiazol-1-yl)-3,3-dimethylbutan-2-yl N-[(3S)-2-oxo-1-(pyridine-2-sulfonamido)heptan-3-yl]carbamate	IC50	40 nM
CA-074	IC50	40 nM
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]pyrrolidine-2-carboxamide	IC50	43.3 nM	US-8729061: Pyrrolidine derivatives
N-[(2S)-1-[(1-cyanocyclopropyl)amino]-4,4-difluoro-1-oxopentan-2-yl]-8-azaspiro[4.5]decane-8-carboxamide	KI	44 nM	US-8609681: Spirocyclic nitriles as protease inhibitors
(2S,4R)-1-[1-(4-bromophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]pyrrolidine-2-carboxamide	IC50	45.4 nM	US-8729061: Pyrrolidine derivatives
N-[(2S)-1-[(1-cyanocyclopropyl)amino]-4,4-difluoro-1-oxopentan-2-yl]-3-azaspiro[5.5]undecane-3-carboxamide	KI	46 nM	US-8609681: Spirocyclic nitriles as protease inhibitors
benzyl N-[(2S)-4-methyl-1-{3-[(2S)-4-methyl-2-(quinolin-7-ylformamido)pentanamido]-4-oxopyrrolidin-1-yl}pentan-2-yl]carbamate	KI	46 nM
(2S,4R)-N-[(3S)-1-(butylamino)-1,2-dioxopentan-3-yl]-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonylpyrrolidine-2-carboxamide	IC50	47.8 nM	US-8729061: Pyrrolidine derivatives
Mercaptomethyl ketone Inhibitor, 47	KI	50 nM
Mercaptomethyl ketone Inhibitor, 51	KI	50 nM
(2S)-2-(1-benzofuran-2-ylformamido)-4-methyl-N-[(2S)-3-oxo-4-(pyridine-2-sulfonamido)butan-2-yl]pentanamide	IC50	59 nM
CA-074b	IC50	60 nM
N-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(4-propylpiperazin-1-yl)	EC50	61 nM
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(2-methylpropylamino)-1,2-dioxopentan-3-yl]pyrrolidine-2-carboxamide	IC50	61.6 nM	US-8729061: Pyrrolidine derivatives
N-[(2S)-1-[(1-cyanocyclopropyl)amino]-4,4-difluoro-1-oxoheptan-2-yl]-6-azaspiro[2.5]octane-6-carboxamide	KI	62 nM	US-8609681: Spirocyclic nitriles as protease inhibitors
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(cyclopropylamino)-1,2-dioxopentan-3-yl]pyrrolidine-2-carboxamide	IC50	62.7 nM	US-8729061: Pyrrolidine derivatives
(2S)-3,3-dimethyl-1-{3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}butan-2-yl N-[(3S)-1-[(6-fluoropyridin-2-yl)amino]-2-oxoheptan-3-yl]carbamate	IC50	68 nM
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(2-naphthalen-1-ylethylamino)-1,2-dioxopentan-3-yl]pyrrolidine-2-carboxamide	IC50	68.8 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-1-[1-(4-iodophenyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide	IC50	70.1 nM	US-8729061: Pyrrolidine derivatives
(2S)-1-(5,6-dichloro-1H-1,3-benzodiazol-1-yl)-3,3-dimethylbutan-2-yl N-[(2S)-3-oxo-4-(pyridine-2-sulfonamido)butan-2-yl]carbamate	IC50	71 nM
(2S)-3,3-dimethyl-1-{4-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}butan-2-yl N-[(3S)-2-oxo-1-(pyridine-2-sulfonamido)heptan-3-yl]carbamate	IC50	72 nM
1-Ethyl-6-methyl-3-thiophen-2-yl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	IC50	72.2 nM
(2S,4R)-N-[(3S)-1-(benzylamino)-1,2-dioxopentan-3-yl]-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonylpyrrolidine-2-carboxamide	IC50	77 nM	US-8729061: Pyrrolidine derivatives
(2S)-3,3-dimethyl-1-[3-(pyridin-3-yl)-1H-pyrazol-1-yl]butan-2-yl N-[(3S)-2-oxo-1-(pyridine-2-sulfonamido)heptan-3-yl]carbamate	IC50	79 nM
(2S,4R)-4-(2-chloro-4-fluorophenyl)sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]pyrrolidine-2-carboxamide	IC50	83.2 nM	US-8729061: Pyrrolidine derivatives
N-[(2S)-1-[(1-cyanocyclopropyl)amino]-4,4-difluoro-1-oxoheptan-2-yl]-9-cyclopropyl-3,9-diazaspiro[5.5]undecane-3-carboxamide	KI	84 nM	US-8609681: Spirocyclic nitriles as protease inhibitors
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(2-methoxyethylamino)-1,2-dioxopentan-3-yl]pyrrolidine-2-carboxamide	IC50	85.4 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-4-(2-chloro-4-morpholin-4-ylphenyl)sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]pyrrolidine-2-carboxamide	IC50	93.2 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(cyclopropylamino)-4-methyl-1,2-dioxopentan-3-yl]pyrrolidine-2-carboxamide	IC50	97.3 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-1-[1-(4-bromophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(cyclopropylamino)-1,2-dioxopentan-3-yl]pyrrolidine-2-carboxamide	IC50	98.5 nM	US-8729061: Pyrrolidine derivatives
N-[(2S)-1-[(4-cyano-1-methylpiperidin-4-yl)amino]-4,4-difluoro-1-oxopentan-2-yl]-6-azaspiro[2.5]octane-6-carboxamide	KI	99 nM	US-8609681: Spirocyclic nitriles as protease inhibitors
N-[(2S)-1-[(1-cyanocyclopropyl)amino]-4,4-difluoro-1-oxo-5-phenylpentan-2-yl]-9-cyclopropyl-3,9-diazaspiro[5.5]undecane-3-carboxamide	KI	100 nM	US-8609681: Spirocyclic nitriles as protease inhibitors
benzyl N-[(1S)-2-methyl-1-[(1-oxo-3-phenylpropan-2-yl)carbamoyl]propyl]carbamate	IC50	100 nM
(2S,4R)-4-(2-chloro-4-morpholin-4-ylphenyl)sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxopentan-3-yl]pyrrolidine-2-carboxamide	IC50	101 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(cyclopropylamino)-1,2-dioxopentan-3-yl]-1-[1-(4-iodophenyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide	IC50	107 nM	US-8729061: Pyrrolidine derivatives
(2S,4R)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-N-[(3S)-1-(ethylamino)-1,2-dioxohexan-3-yl]pyrrolidine-2-carboxamide	IC50	108 nM	US-8729061: Pyrrolidine derivatives

ChEMBL bioactivities

1220 potent at pChembl≥5 of 1553 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	CHEMBL2028921
10.11	Ki	0.077	nM	CHEMBL190121
10.06	Ki	0.088	nM	CHEMBL2028907
9.92	Ki	0.12	nM	CHEMBL2028909
9.89	Ki	0.13	nM	CHEMBL2028910
9.60	Ki	0.25	nM	CHEMBL191558
9.60	Ki	0.25	nM	CHEMBL2028919
9.52	Ki	0.3	nM	CHEMBL2028911
9.44	Ki	0.36	nM	CHEMBL1651361
9.42	Ki	0.38	nM	CHEMBL1651353
9.39	Ki	0.406	nM	CHEMBL3342185
9.37	Ki	0.43	nM	CHEMBL608115
9.34	Ki	0.459	nM	CHEMBL3342184
9.32	Ki	0.48	nM	CHEMBL1651352
9.19	Ki	0.65	nM	CHEMBL1651354
9.17	Ki	0.68	nM	CHEMBL604281
9.16	Ki	0.69	nM	CHEMBL4442025
9.06	Ki	0.88	nM	CHEMBL1651351
9.00	Ki	1	nM	CHEMBL314442
9.00	IC50	1	nM	CHEMBL390474
8.89	Ki	1.3	nM	CHEMBL371420
8.89	Ki	1.3	nM	CHEMBL1651355
8.89	Ki	1.3	nM	CHEMBL1651357
8.85	Ki	1.41	nM	CHEMBL2028912
8.80	Ki	1.6	nM	CHEMBL86453
8.80	Ki	1.58	nM	CHEMBL2028920
8.74	IC50	1.8	nM	CHEMBL336228
8.70	IC50	2	nM	CHEMBL138499
8.70	Ki	2	nM	CHEMBL207347
8.70	IC50	2	nM	CHEMBL390475
8.70	Ki	2	nM	CHEMBL4440655
8.70	Ki	2	nM	CHEMBL271004
8.65	IC50	2.24	nM	CHEMBL490920
8.64	IC50	2.28	nM	CHEMBL4533469
8.62	IC50	2.4	nM	CHEMBL183812
8.62	Ki	2.4	nM	CHEMBL1651349
8.62	Ki	2.4	nM	CHEMBL1651350
8.61	IC50	2.44	nM	CHEMBL490920
8.55	Ki	2.8	nM	CHEMBL1651356
8.52	IC50	3	nM	CHEMBL222649
8.51	IC50	3.11	nM	CHEMBL521636
8.47	Ki	3.36	nM	E-64C
8.45	Ki	3.56	nM	CHEMBL3342183
8.43	Ki	3.7	nM	CHEMBL314777
8.43	IC50	3.7	nM	CHEMBL490920
8.40	Ki	4	nM	CHEMBL264623
8.40	Ki	4	nM	CHEMBL89100
8.39	IC50	4.1	nM	CHEMBL131688
8.37	Ki	4.3	nM	CHEMBL1651242
8.34	IC50	4.6	nM	E-64

PubChem BioAssay actives

1219 with measured affinity, of 3992 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
methyl (2S)-2-[[(2S,3S)-2-[[[(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-4-methyl-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]pentanoyl]amino]propanoyl]amino]carbamoylamino]-3-methylpentanoyl]amino]-3-methylbutanoate	50286: Inhibition of Human Cathepsin B	ki	<0.0001	uM
methyl (2S)-2-[[(2S,3S)-2-[[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]carbamoylamino]-3-methylpentanoyl]amino]-3-methylbutanoate	50286: Inhibition of Human Cathepsin B	ki	0.0001	uM
methyl (2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-[[[(2S)-2-[[(2S)-4-methyl-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]pentanoyl]amino]-3-phenylpropanoyl]amino]carbamoylamino]pentanoyl]amino]butanoate	50286: Inhibition of Human Cathepsin B	ki	0.0001	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-1-[2-[[(2S)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]hydrazinyl]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamate	50286: Inhibition of Human Cathepsin B	ki	0.0001	uM
[(2S)-1-cyclohexylpropan-2-yl] N-[cyano(methyl)amino]carbamate	239257: Inhibition constant against human cathepsin B in fluorescence assay using Cbz-Phe-Arg-AMC	ki	0.0001	uM
N-[(2S)-3-cyclohexyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]propan-2-yl]-1H-indole-2-carboxamide	1805744: FRET-based enzymatic assay from Article 10.1021/jacs.1c08060: “Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity.”	ic50	0.0002	uM
methyl (2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-[[[(2S,3S)-3-methyl-2-[[(2S)-4-methyl-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]pentanoyl]amino]pentanoyl]amino]carbamoylamino]pentanoyl]amino]butanoate	50286: Inhibition of Human Cathepsin B	ki	0.0003	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-1-[2-[[(2S,3S)-1-[[(2S)-1-(benzylamino)-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]hydrazinyl]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]carbamate	50286: Inhibition of Human Cathepsin B	ki	0.0003	uM
[(2S)-1-phenylbutan-2-yl] N-[cyano(methyl)amino]carbamate	239257: Inhibition constant against human cathepsin B in fluorescence assay using Cbz-Phe-Arg-AMC	ki	0.0003	uM
tert-butyl N-[cyano-[2-(dibenzylamino)-2-oxoethyl]amino]carbamate	1168921: Inhibition of human cathepsin B using Z-Arg-Arg-pNA chromogenic substrate fluorogenic substrate incubated for 30 mins	ki	0.0004	uM
benzyl N-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]carbamate	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0004	uM
benzyl N-[(2S)-1-[[cyano(methyl)amino]-methylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0004	uM
N-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-4-(5-thiophen-2-yl-1,2,4-oxadiazol-3-yl)benzamide	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0004	uM
tert-butyl N-[[2-[benzyl(methyl)amino]-2-oxoethyl]-cyanoamino]carbamate	1168921: Inhibition of human cathepsin B using Z-Arg-Arg-pNA chromogenic substrate fluorogenic substrate incubated for 30 mins	ki	0.0005	uM
(4-butylcyclohexyl) N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate	1805744: FRET-based enzymatic assay from Article 10.1021/jacs.1c08060: “Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity.”	ic50	0.0005	uM
(4,4-difluorocyclohexyl)methyl N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate	1805744: FRET-based enzymatic assay from Article 10.1021/jacs.1c08060: “Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity.”	ic50	0.0005	uM
benzyl N-[(2S)-1-[[cyano(methyl)amino]-methylamino]-3-cyclohexyl-1-oxopropan-2-yl]carbamate	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0005	uM
1-benzyl-3-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]urea	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0006	uM
benzyl N-[(2S)-1-[[cyano(methyl)amino]-methylamino]-1-oxo-3-phenylpropan-2-yl]carbamate	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0007	uM
N-[1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-4-(4-phenylphenyl)benzamide	1545144: Inhibition of human liver cathepsin B using Z-Phe-Arg-AMC as substrate incubated for 30 mins by fluorescence based assay	ki	0.0007	uM
benzyl N-[(2S,3S)-1-[[cyano(methyl)amino]-methylamino]-3-methyl-1-oxopentan-2-yl]carbamate	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0009	uM
(4S,5R)-4-(2,3-dimethylphenoxy)-6-oxa-1-azabicyclo[3.2.1]octan-7-one	290151: Inhibition of human recombinant cathepsin B	ic50	0.0010	uM
[(2S)-1-cyclohexylpropan-2-yl] N-[cyano(propan-2-yl)amino]carbamate	239257: Inhibition constant against human cathepsin B in fluorescence assay using Cbz-Phe-Arg-AMC	ki	0.0013	uM
1-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-3-phenylurea	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0013	uM
1-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-3-[[4-(5-thiophen-2-yl-1,2,4-oxadiazol-3-yl)phenyl]methyl]urea	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0013	uM
methyl (2S)-2-[[(2S,3S)-2-[[[(2S)-3-(4-methoxyphenyl)-2-[[(2S)-4-methyl-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]pentanoyl]amino]propanoyl]amino]carbamoylamino]-3-methylpentanoyl]amino]-3-methylbutanoate	50286: Inhibition of Human Cathepsin B	ki	0.0014	uM
(3S,3aS,6aR)-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-2-[(2S)-3,3-dimethyl-2-[[(2S)-3-methyl-2-(pyrazine-2-carbonylamino)butanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide	50485: Inhibitory activity against cathepsin B	ki	0.0016	uM
methyl (2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-[[[(2S)-2-[[(2S)-4-methyl-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]pentanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]carbamoylamino]pentanoyl]amino]butanoate	50286: Inhibition of Human Cathepsin B	ki	0.0016	uM
3-[[(2R)-2-cyano-2-[[(2S)-2-[(2,2-diphenylacetyl)amino]-3-(3-methylphenyl)propanoyl]amino]ethoxy]methyl]benzoic acid	1545143: Inhibition of recombinant human cathepsin B expressed in baculovirus expression system using Z-Arg-Arg-AMC as substrate incubated for 20 mins by fluorescence based assay	ic50	0.0018	uM
3-[[(2R)-2-[[(2S)-2-[(4-chloro-2-fluorobenzoyl)amino]-3-(3-methylphenyl)propanoyl]amino]-2-cyanoethoxy]methyl]benzoic acid	50267: Inhibitory activity against recombinant human cathepsin B (cat B) expressed in baculovirus.	ic50	0.0020	uM
2-[(3S)-7-amino-3-[[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]amino]-2-oxoheptyl]sulfanylacetic acid	1799895: Fluorometric High-Throughput Assay from Article 10.1021/cc034008r: “Synthesis of a diverse library of mechanism-based cysteine protease inhibitors.”	ki	0.0020	uM
(4S,5R)-4-phenylmethoxy-6-oxa-1-azabicyclo[3.2.1]octan-7-one	290151: Inhibition of human recombinant cathepsin B	ic50	0.0020	uM
benzyl (2S)-2-[[(2S)-1-[5-(furan-2-yl)-1,3,4-oxadiazol-2-yl]-1-oxopentan-2-yl]carbamoyl]-4-methylpentanoate	266477: Inhibition of human cathepsin B	ki	0.0020	uM
benzyl N-[(3S)-1-[[(2S)-1-[5-(furan-2-yl)-1,3,4-oxadiazol-2-yl]-1-oxohexan-2-yl]amino]-5-methyl-1,2-dioxohexan-3-yl]carbamate	321238: Inhibition of human liver cathepsin B	ki	0.0020	uM
4-bromo-N-[1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]benzamide	1545144: Inhibition of human liver cathepsin B using Z-Phe-Arg-AMC as substrate incubated for 30 mins by fluorescence based assay	ki	0.0020	uM
(2S)-1-[(2S,3S)-3-methyl-2-[[(2S,3S)-3-(propylcarbamoyl)oxirane-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carboxylic acid	1545139: Inhibition of cathepsin B (unknown origin) assessed as reduction in 7-amino-4-methylcoumarin formation using Z-Arg-Arg-MCA as substrate preincubated for 3 mins followed by substrate addition and measured after 10 mins by fluorescence spectrometric method	ic50	0.0022	uM
(2S)-1-[(2S,3S)-2-[[(2S,3S)-3-ethoxycarbonyloxirane-2-carbonyl]amino]-3-methylpentanoyl]pyrrolidine-2-carboxylic acid	1545139: Inhibition of cathepsin B (unknown origin) assessed as reduction in 7-amino-4-methylcoumarin formation using Z-Arg-Arg-MCA as substrate preincubated for 3 mins followed by substrate addition and measured after 10 mins by fluorescence spectrometric method	ic50	0.0023	uM
[(2S)-1-cyclohexylpropan-2-yl] 1-cyanoazetidine-2-carboxylate	241949: Inhibitory concentration against human cathepsin B using 10 uM Cbz-Phe-Arg-AMC	ic50	0.0024	uM
1-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]urea	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0024	uM
1-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-3-[4-(5-thiophen-2-yl-1,2,4-oxadiazol-3-yl)phenyl]urea	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0024	uM
1-[(2S)-1-[[cyano(methyl)amino]-methylamino]-4-methyl-1-oxopentan-2-yl]-3-[[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]methyl]urea	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0028	uM
N-[(2R)-1-[[(E,3R)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]amino]-4-methyl-1-oxopentan-2-yl]morpholine-4-carboxamide	747796: Inhibition of human cathepsin-B	ic50	0.0030	uM
3-acetyl-2-(4-tert-butylanilino)-8-chloro-6-nitro-1H-quinolin-4-one	350737: Inhibition of human liver cathepsin B after 30 mins by fluorometric end-point assay	ic50	0.0031	uM
(2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid	647095: Inhibition of cathepsin B	ki	0.0034	uM
tert-butyl N-[cyano-(2-morpholin-4-yl-2-oxoethyl)amino]carbamate	1168921: Inhibition of human cathepsin B using Z-Arg-Arg-pNA chromogenic substrate fluorogenic substrate incubated for 30 mins	ki	0.0036	uM
(3S,3aS,6aR)-N-[(3S)-1-(butan-2-ylamino)-1,2-dioxohexan-3-yl]-2-[(2S)-3,3-dimethyl-2-[[(2S)-3-methyl-2-(pyrazine-2-carbonylamino)butanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide	50485: Inhibitory activity against cathepsin B	ki	0.0037	uM
(3S,3aS,6aR)-N-[1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-2-[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(pyrazine-2-carbonylamino)butanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide	50485: Inhibitory activity against cathepsin B	ki	0.0040	uM
(2R)-N-[(2S)-6-(benzenesulfonamido)-1-oxohexan-2-yl]-2-(methanesulfonamido)-3-phenylmethoxypropanamide	50287: Inhibitory activity against cathepsin B receptor in human liver	ki	0.0040	uM
5-[[(2R)-2-cyano-2-[[(2S)-3-(3-methylphenyl)-2-[(3-oxo-1H-2-benzofuran-5-yl)amino]propanoyl]amino]ethoxy]methyl]-2-fluorobenzoic acid	50468: Inhibitory activity against cathepsin B (catB)	ic50	0.0041	uM
benzyl N-[(2S)-1-[[cyano(methyl)amino]-methylamino]-3-methyl-1-oxobutan-2-yl]carbamate	554257: Inhibition of human recombinant cathepsin B after 30 mins by spectrophotometric assay	ki	0.0043	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
CA 074 methyl ester	affects cotreatment, decreases expression, decreases reaction, increases expression, increases cleavage (+2 more)	7
Arsenic Trioxide	decreases activity, affects reaction, affects cotreatment, increases expression, decreases expression (+4 more)	7
bisphenol A	decreases reaction, increases expression, affects expression, affects methylation, decreases expression	6
Valproic Acid	affects expression, increases expression	5
3-methyladenine	decreases reaction, increases expression, affects cotreatment, increases activity, increases secretion	4
Acetylcysteine	increases secretion, increases abundance, affects cotreatment, increases expression, decreases reaction	4
Calcitriol	increases expression	4
Chloroquine	decreases reaction, increases activity, decreases activity, increases transport, affects cotreatment (+2 more)	4
Doxorubicin	affects binding, increases cleavage, affects expression, decreases expression	4
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction, increases expression	4
Acetaminophen	decreases expression, increases expression	3
Cannabidiol	decreases expression, increases expression	3
Estradiol	increases expression, affects cotreatment, decreases reaction	3
sodium arsenite	increases expression	2
cobaltous chloride	affects cotreatment, decreases reaction, increases activity	2
bafilomycin A1	affects cotreatment, decreases reaction, increases activity, affects localization	2
leucyl-leucine-methyl ester	decreases activity, increases expression	2
chloropicrin	decreases expression	2
aloxistatin	affects cotreatment, decreases expression, decreases reaction, increases degradation	2
lipopolysaccharide, Escherichia coli O111 B4	decreases reaction, increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Fulvestrant	decreases reaction, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
alpha-Chlorohydrin	decreases expression, decreases reaction	2
Vehicle Emissions	increases expression, affects expression, increases reaction, increases abundance	2
Cadmium	increases palmitoylation, increases expression, affects reaction, decreases reaction, increases abundance	2
Dinitrochlorobenzene	affects binding, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Phenytoin	decreases activity, increases expression	2

ChEMBL screening assays

610 unique, capped per target: 577 binding, 25 admet, 5 toxicity, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5106297	Binding	Selectivity ratio of IC50 for Cathepsin B (unknown origin) to IC50 for Cathepsin K (unknown origin)	Lead optimization of cathepsin K inhibitors for the treatment of Osteoarthritis. — Bioorg Med Chem Lett
CHEMBL4041064	ADMET	Inhibition of human liver cathepsin B using Z-Phe-Arg-AMC as substrate by kinetic fluorescence assay	Discovery of Novel and Highly Selective Inhibitors of Calpain for the Treatment of Alzheimer’s Disease: 2-(3-Phenyl-1H-pyrazol-1-yl)-nicotinamides. — J Med Chem
CHEMBL5154224	Toxicity	Inhibition of human cathepsin B using Z-Leu-Arg-AMC as substrate by FRET assay	Discovery and Crystallographic Studies of Nonpeptidic Piperazine Derivatives as Covalent SARS-CoV-2 Main Protease Inhibitors. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7WU	Abcam Raji CTSB KO	Cancer cell line	Male
CVCL_B9XD	Abcam THP-1 CTSB KO	Cancer cell line	Male
CVCL_C6ZA	Abcam PC-3 CTSB KO	Cancer cell line	Male
CVCL_E0BB	Ubigene HeLa CTSB KO	Cancer cell line	Female
CVCL_F1NT	HyCyte GES-1 KO-hCTSB	Transformed cell line	Sex unspecified
CVCL_SK16	HAP1 CTSB (-) 1	Cancer cell line	Male
CVCL_XN02	HAP1 CTSB (-) 2	Cancer cell line	Male
CVCL_XN03	HAP1 CTSB (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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