CTRB1

Summary

CTRB1 (chymotrypsinogen B1, HGNC:2521) is a protein-coding gene on chromosome 16q23.1, encoding Chymotrypsinogen B (P17538).

This gene encodes a member of the serine protease family of enzymes and forms a principal precursor of the pancreatic proteolytic enzymes. The encoded preproprotein is synthesized in the acinar cells of the pancreas and secreted into the small intestine where it undergoes proteolytic activation to generate a functional enzyme. This CTRB1 gene is located head-to-head with the related CTRB2 gene. Some human populations have an alternate haplotype which inverts a 16.6 Kb region containing portions of intron 1, exon 1, and the upstream sequence of the CTRB1 and CTRB2 genes. In this inversion haplotype exon 1 and flanking sequence is swapped in CTRB1 and CTRB2. This inversion is associated with differential gene expression and increased risk for chronic pancreatitis. The GRCh38 assembly represents the minor allele for SNP rs8048956 of the CTRB1 gene. SNP rs8048956 in intron 1 of the CTRB2 gene is diagnostic for this inversion. This CTRB1 gene encodes distinct isoforms, some or all of which may undergo similar processing to generate the mature protein.

Source: NCBI Gene 1504 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 68 total
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2521
Approved symbol	CTRB1
Name	chymotrypsinogen B1
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168925
Ensembl biotype	protein_coding
OMIM	118890
Entrez	1504

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000361017, ENST00000495583, ENST00000642378

RefSeq mRNA: 2 — MANE Select: NM_001906 NM_001329190, NM_001906

CCDS: CCDS32490

Canonical transcript exons

ENST00000361017 — 7 exons

Exon	Start	End
ENSE00001403143	75224705	75224924
ENSE00002454314	75223448	75223628
ENSE00002466081	75224055	75224188
ENSE00002475183	75222768	75222871
ENSE00002489329	75223141	75223219
ENSE00002517123	75222969	75223048
ENSE00002615660	75218988	75219059

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1125 / max 3294.1180, expressed in 14 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158140	173.6375	30
155022	58.6852	25
155020	1.0510	8
158141	0.9501	6
155021	0.7996	4
155023	0.4394	9
207953	0.2082	3
207955	0.1614	3
207954	0.1460	3
207968	0.0901	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.99	gold quality
pancreas	UBERON:0001264	98.72	gold quality
islet of Langerhans	UBERON:0000006	96.16	gold quality
duodenum	UBERON:0002114	88.98	gold quality
fundus of stomach	UBERON:0001160	83.08	gold quality
right coronary artery	UBERON:0001625	81.91	gold quality
ectocervix	UBERON:0012249	80.31	gold quality
right uterine tube	UBERON:0001302	79.93	gold quality
endocervix	UBERON:0000458	77.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.81	gold quality
right adrenal gland	UBERON:0001233	77.25	gold quality
right lobe of liver	UBERON:0001114	77.10	gold quality
left uterine tube	UBERON:0001303	77.07	gold quality
spleen	UBERON:0002106	77.00	gold quality
lower esophagus mucosa	UBERON:0035834	76.98	gold quality
descending thoracic aorta	UBERON:0002345	76.49	gold quality
right adrenal gland cortex	UBERON:0035827	76.12	gold quality
metanephros cortex	UBERON:0010533	74.67	gold quality
left adrenal gland	UBERON:0001234	74.40	gold quality
uterine cervix	UBERON:0000002	73.91	gold quality
placenta	UBERON:0001987	73.84	gold quality
thoracic aorta	UBERON:0001515	73.38	gold quality
body of stomach	UBERON:0001161	73.33	gold quality
ascending aorta	UBERON:0001496	72.65	gold quality
pituitary gland	UBERON:0000007	71.70	gold quality
left adrenal gland cortex	UBERON:0035825	71.58	gold quality
right ovary	UBERON:0002118	70.76	gold quality
apex of heart	UBERON:0002098	70.05	gold quality
adrenal gland	UBERON:0002369	69.68	gold quality
transverse colon	UBERON:0001157	69.50	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	18558.37
E-MTAB-5061	yes	9764.01
E-ENAD-27	yes	6692.87
E-GEOD-83139	yes	2582.77
E-HCAD-31	yes	5.29
E-GEOD-109979	no	6.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Two protective, low-frequency, non-synonymous variants were significantly associated with a decrease in age-related macular degeneration (AMD)risk: A307V in PELI3 and N1050Y in CFH .We also identified a strong protective signal for a common variant (rs8056814) near CTRB1 associated with a decrease in AMD risk (logistic regression: OR = 0.71, P = 1.8 x 10-07). (PMID:28011711)
• An inversion in the CTRB1-CTRB2 locus modifies risk for Alcoholic and Non-alcoholic Chronic Pancreatitis indicating that common pathomechanisms are involved in these inflammatory disorders. (PMID:28754779)
• Sequencing of the complex CTRB1-CTRB2 locus in chronic pancreatitis. (PMID:33036922)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctrb.3	ENSDARG00000039730
danio_rerio	ctrb.1	ENSDARG00000090428
danio_rerio	ctrb.2	ENSDARG00000093844
mus_musculus	Ctrb1	ENSMUSG00000031957
rattus_norvegicus	Ctrb1	ENSRNOG00000019068
drosophila_melanogaster	CG11912	FBGN0031248

Paralogs (2): CTRC (ENSG00000162438), CTRB2 (ENSG00000168928)

Protein

Protein identifiers

Chymotrypsinogen B — P17538 (reviewed: P17538)

All UniProt accessions (3): P17538, A0A2R8Y4E9, J3QKZ2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Extracellular space.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (2): NP_001316119, NP_001897* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

UniProt features (19 total): disulfide bond 5, chain 4, active site 3, sequence variant 2, sequence conflict 2, signal peptide 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17538-F1	91.90	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): 75 (charge relay system); 120 (charge relay system); 213 (charge relay system)

Post-translational modifications (1): 93

Disulfide bonds (5): 19–140, 60–76, 154–219, 186–200, 209–238

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-9758881	Uptake of dietary cobalamins into enterocytes

MSigDB gene sets: 38 (showing top): GOBP_DIGESTION, MORF_WNT1, ZHONG_SECRETOME_OF_LUNG_CANCER_AND_FIBROBLAST, RIZKI_TUMOR_INVASIVENESS_3D_UP, SANSOM_APC_TARGETS, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS, WUNDER_INFLAMMATORY_RESPONSE_AND_CHOLESTEROL_UP, MODULE_49, BILANGES_SERUM_SENSITIVE_GENES, ROESSLER_LIVER_CANCER_METASTASIS_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, AKT_UP.V1_UP, MTOR_UP.V1_UP

GO Biological Process (2): proteolysis (GO:0006508), digestion (GO:0007586)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Degradation of the extracellular matrix	1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
multicellular organismal process	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTRB1	SERPINA3	P01011	969
CTRB1	SERPINA1	P01009	957
CTRB1	SPINK1	P00995	866
CTRB1	A2M	P01023	846
CTRB1	AMY2A	P04746	845
CTRB1	AMY1B	P04745	836
CTRB1	AMY2B	P19961	835
CTRB1	ALB	P02768	822
CTRB1	SLPI	P03973	782
CTRB1	A2ML1	A8K2U0	780
CTRB1	GBA1	P04062	773
CTRB1	PNLIP	P16233	763
CTRB1	PZP	P20742	755
CTRB1	DNAJC1	Q96KC8	754
CTRB1	INS	P01308	736

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CTRB1	PNMA2	psi-mi:“MI:0915”(physical association)	0.590
CTRB2	CTRB1	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A1KXI1, C0HKA5, C0HKA6, C0HKF7, C0HKF8, C6ZDB5, O97370, O97398, O97399, P00765, P00766, P00768, P04814, P07338, P07477, P07478, P17538, P29786, P29787, P35005, P35035, P35037, P35038, P35039, P35040, P35041, P35044, P35048, P35049, P35587, P35588, P36178, P39675, P42278, P42279, P42280, P47796, P49275, P51588, P52905

Diamond homologs: A0A182C2Z2, B8V7S0, O08762, O60235, P00747, P00760, P00762, P00765, P00766, P00767, P00774, P03951, P03952, P04070, P04813, P05981, P06867, P06871, P06872, P07146, P07338, P07477, P08217, P08426, P08519, P12545, P14272, P15944, P17538, P19799, P20231, P20918, P26262, P27435, P29786, P35033, P40313, P47796, P50342, P56677

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

908 predictions. Top by Δscore:

Variant	Effect	Δscore
16:75222967:A:AG	acceptor_gain	1.0000
16:75222967:AG:A	acceptor_gain	1.0000
16:75222968:G:GT	acceptor_gain	1.0000
16:75222968:GG:G	acceptor_gain	1.0000
16:75222968:GGA:G	acceptor_gain	1.0000
16:75222968:GGAC:G	acceptor_gain	1.0000
16:75222968:GGACA:G	acceptor_gain	1.0000
16:75223045:TCAG:T	donor_loss	1.0000
16:75223046:CAG:C	donor_loss	1.0000
16:75223047:AGG:A	donor_loss	1.0000
16:75223048:GG:G	donor_loss	1.0000
16:75223049:G:C	donor_loss	1.0000
16:75223050:T:G	donor_loss	1.0000
16:75223219:GGTA:G	donor_loss	1.0000
16:75223441:C:G	acceptor_gain	1.0000
16:75223443:CCCA:C	acceptor_loss	1.0000
16:75223444:CCAG:C	acceptor_loss	1.0000
16:75223446:A:AG	acceptor_gain	1.0000
16:75223446:A:C	acceptor_loss	1.0000
16:75223447:G:GG	acceptor_gain	1.0000
16:75223612:C:T	donor_gain	1.0000
16:75223627:CGG:C	donor_loss	1.0000
16:75223629:G:GG	donor_gain	1.0000
16:75223629:GTGAG:G	donor_loss	1.0000
16:75224053:A:AG	acceptor_gain	1.0000
16:75224054:G:A	acceptor_loss	1.0000
16:75224054:G:GT	acceptor_gain	1.0000
16:75224054:GC:G	acceptor_gain	1.0000
16:75224054:GCC:G	acceptor_gain	1.0000
16:75224054:GCCA:G	acceptor_gain	1.0000

AlphaMissense

1714 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:75223609:G:C	W159C	0.998
16:75223609:G:T	W159C	0.998
16:75222854:T:A	W47R	0.993
16:75222854:T:C	W47R	0.993
16:75222856:G:C	W47C	0.993
16:75222856:G:T	W47C	0.993
16:75223491:A:T	D120V	0.993
16:75224156:T:A	C200S	0.993
16:75224157:G:C	C200S	0.993
16:75224709:A:T	D212V	0.993
16:75222991:G:A	C60Y	0.992
16:75223491:A:C	D120A	0.992
16:75223607:T:A	W159R	0.992
16:75223607:T:C	W159R	0.992
16:75224114:T:A	C186S	0.991
16:75224115:G:C	C186S	0.991
16:75224157:G:A	C200Y	0.991
16:75223490:G:C	D120H	0.990
16:75224158:T:G	C200W	0.990
16:75224709:A:C	D212A	0.990
16:75222863:T:C	S50P	0.989
16:75224708:G:C	D212H	0.989
16:75223594:T:G	C154W	0.988
16:75224710:C:A	D212E	0.988
16:75224710:C:G	D212E	0.988
16:75222990:T:A	C60S	0.987
16:75222991:G:C	C60S	0.987
16:75223492:C:A	D120E	0.987
16:75223492:C:G	D120E	0.987
16:75223592:T:C	C154R	0.987

dbSNP variants (sampled 300 via entrez): RS1000012029 (16:75206239 C>G), RS1000089786 (16:75221789 A>G), RS1000463830 (16:75219670 T>C), RS1000486996 (16:75223319 G>A), RS1000715297 (16:75209061 C>G), RS1000754737 (16:75223719 T>C), RS1000927968 (16:75222511 T>G), RS1001457207 (16:75206662 T>C), RS1001553982 (16:75224409 GCCCT>G), RS1001665440 (16:75208228 A>G), RS1001748007 (16:75219999 GTTTTGGTTTT>G), RS1001921389 (16:75224210 C>T), RS1001971380 (16:75221546 G>C), RS1002122587 (16:75217517 C>A,T), RS1002476655 (16:75218038 T>C,G)

Disease associations

OMIM: gene MIM:118890 | disease phenotypes:

GenCC curated gene-disease

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

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

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002553_10	Pancreatic cancer	1.000000e-10
GCST003219_12	Advanced age-related macular degeneration	5.000000e-12
GCST004860_122	Alcoholic chronic pancreatitis	4.000000e-09
GCST004860_124	Alcoholic chronic pancreatitis	8.000000e-07
GCST004860_129	Alcoholic chronic pancreatitis	8.000000e-07
GCST004860_136	Alcoholic chronic pancreatitis	2.000000e-06
GCST004860_137	Alcoholic chronic pancreatitis	7.000000e-06
GCST004860_154	Alcoholic chronic pancreatitis	1.000000e-07
GCST004860_62	Alcoholic chronic pancreatitis	5.000000e-06
GCST006867_134	Type 2 diabetes	2.000000e-18
GCST007612_2	Chronic obstructive pulmonary disease or coronary artery disease (pleiotropy)	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523987 (PROTEIN FAMILY), CHEMBL4796 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 94,386 (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
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL50	QUERCETIN	3	74,559
CHEMBL599552	INDIGO	3	6,024
CHEMBL1160008	IODOPHTHALEIN	2	67
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL206335	RAZAXABAN	2	301

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7202877	Efficacy	4	sitagliptin;vildagliptin	Diabetes Mellitus;Type 2

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
beta ph61	Inhibition	8.28	pKi

ChEMBL bioactivities

90 potent at pChembl≥5 of 111 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.38	Ki	0.42	nM	CHEMBL4450993
9.06	Ki	0.88	nM	CHEMBL4586444
8.82	Ki	1.5	nM	CHEMBL4469390
8.68	IC50	2.1	nM	CHEMBL108540
8.28	IC50	5.3	nM	CHEMBL335675
8.28	Ki	5.3	nM	CHEMBL307448
7.96	Ki	11	nM	CHEMBL4590739
7.92	IC50	12	nM	CHEMBL436591
7.82	IC50	15	nM	CHEMBL134816
7.82	IC50	15	nM	CHEMBL2409452
7.77	Ki	17	nM	CHEMBL132171
7.75	IC50	18	nM	CHEMBL134821
7.70	Ki	20	nM	CHEMBL4638245
7.68	IC50	21	nM	CHEMBL2409457
7.51	IC50	31	nM	CHEMBL424453
7.51	IC50	31	nM	CHEMBL2409451
7.46	Ki	35	nM	MILVEXIAN
7.42	IC50	38	nM	CHEMBL2409445
7.40	IC50	40	nM	CHEMBL2409456
7.36	IC50	44	nM	CHEMBL135080
7.34	IC50	46	nM	CHEMBL2409458
7.31	IC50	49	nM	CHEMBL131704
7.19	IC50	65	nM	CHEMBL294771
7.18	IC50	66	nM	CHEMBL2409450
7.14	IC50	72	nM	CHEMBL134068
7.10	Ki	79	nM	CHEMBL130006
7.06	IC50	87	nM	CHEMBL134821
7.06	IC50	88	nM	CHEMBL65148
6.85	IC50	140	nM	CHEMBL134268
6.85	IC50	140	nM	CHEMBL2409571
6.85	IC50	140	nM	CHEMBL65589
6.82	Ki	150	nM	CHEMBL4592765
6.77	IC50	170	nM	CHEMBL2409570
6.75	IC50	180	nM	CHEMBL67023
6.72	IC50	190	nM	CHEMBL336964
6.66	IC50	220	nM	CHEMBL134024
6.60	IC50	250	nM	CHEMBL338962
6.57	Ki	270	nM	CHEMBL60695
6.54	Ki	290	nM	CHEMBL58683
6.50	Ki	320	nM	CHEMBL56732
6.50	Ki	320	nM	BORTEZOMIB
6.48	Ki	330	nM	CHEMBL4560112
6.44	Ki	360	nM	CHEMBL293513
6.43	IC50	370	nM	CHEMBL2409575
6.42	IC50	380	nM	CHEMBL5425314
6.33	Ki	463	nM	CHEMBL4560512
6.28	IC50	530	nM	CHEMBL436591
6.28	Ki	530	nM	CHEMBL213352
6.24	Ki	580	nM	CHEMBL386463
6.19	Ki	650	nM	CHEMBL57262

PubChem BioAssay actives

81 with measured affinity, of 346 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
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-34,49-dibenzyl-4-[(2S)-butan-2-yl]-40-(carboxymethyl)-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-28-methyl-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-19-yl]propanoic acid	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0004	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-benzyl-4-[(2S)-butan-2-yl]-40-(carboxymethyl)-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-19-yl]propanoic acid	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0009	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-34,49-dibenzyl-4-[(2S)-butan-2-yl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-28-methyl-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-19-[(4-phenylphenyl)methyl]-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0015	uM
[3-[(4-cyanobenzoyl)amino]-2,2-dimethyl-5-phenylpentanoyl] 3-[(4-cyanobenzoyl)amino]-2,2-dimethyl-5-phenylpentanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0021	uM
(6E)-6-(iodomethylidene)-4-phenyloxan-2-one	219284: Binding constant alpha-chymotrypsin was determined by competitive inhibition assay with Suc-Ala-Ala-Pro-Phe-pNA as substrate	ki	0.0053	uM
(3-benzamido-2,2-dimethylheptanoyl) 3-benzamido-2,2-dimethylheptanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0053	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-benzyl-19-(2-carboxyethyl)-40-(carboxymethyl)-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-4-yl]propanoic acid	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.0110	uM
[3-(butanoylamino)-2,2-dimethyl-5-phenylpentanoyl] 3-(butanoylamino)-2,2-dimethyl-5-phenylpentanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0120	uM
[3-[(4-cyanobenzoyl)amino]-2,2-dimethyl-3-phenylpropanoyl] 3-[(4-cyanobenzoyl)amino]-2,2-dimethyl-3-phenylpropanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0150	uM
methyl 1-(3-methylbenzoyl)-5-nitroindazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.0150	uM
methyl 4-oxo-4-[[(2S)-1-oxo-1-[[(2S)-1-oxo-1-[(2S)-2-[[(2S)-4,4,4-trifluoro-3-oxo-1-phenylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]propan-2-yl]amino]propan-2-yl]amino]butanoate	219282: Binding affinity against alpha-chymotrypsin	ki	0.0170	uM
(3-benzamido-2,2-dimethyl-5-phenylpentanoyl) 3-benzamido-2,2-dimethyl-5-phenylpentanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0180	uM
methyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	1657784: Inhibition of human chymotrypsin by spectrophotometry	ki	0.0200	uM
ethyl 1-(3-methoxybenzoyl)-5-nitroindazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.0210	uM
(3-benzamido-2,2-dimethyloctanoyl) 3-benzamido-2,2-dimethyloctanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0310	uM
methyl 1-benzoyl-5-nitroindazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.0310	uM
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxopyrimidin-1-yl]-3-(difluoromethyl)-9-methyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one	1817717: Binding affinity to human chymotrypsin assessed as inhibition constant using 3-Carbomethoxypropionyl-L-arginyl-Lprolyl-L-tyrosine p-Nitroaniline as substrate measured upto 120 mins by spectrophotometric analysis	ki	0.0350	uM
methyl 1-(3-methylbenzoyl)-6-nitroindazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.0380	uM
ethyl 1-(3-methylbenzoyl)-5-nitroindazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.0400	uM
(3-benzamido-2,2-dimethylnonanoyl) 3-benzamido-2,2-dimethylnonanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0440	uM
ethyl 5-nitro-1-(thiophene-3-carbonyl)indazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.0460	uM
(3-benzamido-2,2-dimethylhexanoyl) 3-benzamido-2,2-dimethylhexanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0490	uM
1-(3-methylbenzoyl)indazole-3-carbonitrile	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.0660	uM
(3-benzamido-2,2-dimethylpentanoyl) 3-benzamido-2,2-dimethylpentanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.0720	uM
methyl (3S)-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[(4-methoxy-4-oxobutanoyl)amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-2-oxo-4-phenylbutanoate	219282: Binding affinity against alpha-chymotrypsin	ki	0.0790	uM
(3-benzamido-2,2-dimethylpropanoyl) 3-benzamido-2,2-dimethylpropanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.1400	uM
ethyl 1-(3-methylbenzoyl)-5-(propanoylamino)indazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.1400	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-28-(3-amino-3-oxopropyl)-49-benzyl-4-[(2S)-butan-2-yl]-40-(carboxymethyl)-34-[3-(diaminomethylideneamino)propyl]-22-(hydroxymethyl)-25-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-19-yl]propanoic acid	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.1500	uM
ethyl 5-acetamido-1-(3-methylbenzoyl)indazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.1700	uM
[3-[(4-cyanobenzoyl)amino]-2,2-dimethyl-3-(2-methylphenyl)propanoyl] 3-[(4-cyanobenzoyl)amino]-2,2-dimethyl-3-(2-methylphenyl)propanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.1900	uM
[3-[(4-cyanobenzoyl)amino]-3-cyclohex-3-en-1-yl-2,2-dimethylpropanoyl] 3-[(4-cyanobenzoyl)amino]-3-cyclohex-3-en-1-yl-2,2-dimethylpropanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.2200	uM
[3-(2-chlorophenyl)-3-[(4-cyanobenzoyl)amino]-2,2-dimethylpropanoyl] 3-(2-chlorophenyl)-3-[(4-cyanobenzoyl)amino]-2,2-dimethylpropanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.2500	uM
N-[(1R)-1-difluoroboranyl-2-phenylethyl]benzamide	219285: Competitive inhibition of alpha-chymotrypsin	ki	0.2700	uM
2-amino-N-[(1R)-1-difluoroboranyl-2-phenylethyl]propanamide	219285: Competitive inhibition of alpha-chymotrypsin	ki	0.2900	uM
Bortezomib	52603: Inhibitory activity against human Chymotrypsinogen	ki	0.3200	uM
[(1R)-1-(2-aminopropanoylamino)-2-phenylethyl]boronic acid	219285: Competitive inhibition of alpha-chymotrypsin	ki	0.3200	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-28-(3-amino-3-oxopropyl)-49-benzyl-34-(3-carbamimidamidopropyl)-19-(2-carboxyethyl)-40-(carboxymethyl)-25-[(4-chlorophenyl)methyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-4-yl]propanoic acid	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.3300	uM
[(1R)-1-benzamido-2-phenylethyl]boronic acid	219285: Competitive inhibition of alpha-chymotrypsin	ki	0.3600	uM
ethyl 5-(cyclopropanecarbonylamino)-1-(3-methylbenzoyl)indazole-3-carboxylate	762528: Inhibition of human pancreatic chymotrypsin using Suc-Ala-Ala-Pro-7-amino-4-methylcoumarin as substrate by fluorescence microplate reader analysis	ic50	0.3700	uM
3-[5-[(5-chlorothiophen-2-yl)methylamino]-1-(2,2-dimethylpropanoyl)pyrazol-3-yl]-1H-pyridin-2-one	2001900: Inhibition of chymotrypsin (unknown origin)	ic50	0.3800	uM
2-[(1R,4S,7S,13S,19S,22S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4-[(2S)-butan-2-yl]-22-(hydroxymethyl)-19,28-bis[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-34-[(4-phenylphenyl)methyl]-25-propyl-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511316: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate by fluorescence based assay	ki	0.4630	uM
6-[2-fluoro-4-[2-(pyrrolidin-1-ylmethyl)phenyl]phenyl]-1-(4-methoxyphenyl)-7-oxopyrazolo[4,5-d]pyrimidine-3-carboxamide	268422: Binding affinity to chymotrypsin	ki	0.5300	uM
1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-[2-[[(3R)-3-hydroxypyrrolidin-1-yl]methyl]phenyl]phenyl]-3,5-dimethylpyrazolo[4,5-d]pyrimidin-7-one	270188: Binding affinity to human chymotrypsin	ki	0.5800	uM
N-(1-difluoroboranyl-2-phenylethyl)benzamide	219285: Competitive inhibition of alpha-chymotrypsin	ki	0.6500	uM
(1-benzamido-2-phenylethyl)boronic acid	219285: Competitive inhibition of alpha-chymotrypsin	ki	0.6500	uM
[5-[(5-chlorothiophen-2-yl)methylamino]-3-pyridin-2-ylpyrazol-1-yl]-(2-methoxyphenyl)methanone	2001900: Inhibition of chymotrypsin (unknown origin)	ic50	0.6700	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[1-(benzylcarbamoyl)-4-oxoazetidin-2-yl]sulfanyl-4-methylpentan-2-yl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamate	219312: Inhibitory activity against alpha-chymotrypsin	ic50	0.8000	uM
[3-(butanoylamino)-2,2-dimethyloctanoyl] 3-(butanoylamino)-2,2-dimethyloctanoate	219133: Inhibitory activity against bovine pancreatic alpha-chymotrypsin (alpha-CT)	ic50	0.8100	uM
3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-28-(3-amino-3-oxopropyl)-49-benzyl-34-(3-carbamimidamidopropyl)-19-(2-carboxyethyl)-40-(carboxymethyl)-22-(hydroxymethyl)-25-[(4-nitrophenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-4-yl]propanoic acid	1582056: Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate at pH 8 and 298 K measured every 60 secs for 600 secs	ki	0.9200	uM
1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-[2-[(dimethylamino)methyl]phenyl]phenyl]-3,5-dimethylpyrazolo[4,5-d]pyrimidin-7-one	270188: Binding affinity to human chymotrypsin	ki	0.9600	uM

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
aristolochic acid I	increases expression	1
bisphenol A	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

140 unique, capped per target: 109 binding, 24 admet, 6 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4257233	ADMET	Stability of the compound assessed as chymotrypsin (unknown origin)-mediated compound hydrolysis at 250 uM by HPLC analysis	Peptides comprising non-natural amino acids and methods of making and using the same
CHEMBL4307506	Binding	Inhibition of human chymotrypsin using Suc-AAPF-MCA as substrate by fluorescence based assay	Iterative Optimization of the Cyclic Peptide SFTI-1 Yields Potent Inhibitors of Neutrophil Proteinase 3. — ACS Med Chem Lett
CHEMBL4495586	Functional	Chymotrypsin inhibition percentage at 10 µM by FRET kind of response from peptide substrate	Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen

Clinical trials (associated diseases)

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

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