CTRL

Summary

CTRL (chymotrypsin like, HGNC:2524) is a protein-coding gene on chromosome 16q22.1, encoding Chymotrypsin-like protease CTRL-1 (P40313).

This gene encodes a serine-type endopeptidase with chymotrypsin- and elastase-2-like activities. The gene encoding this zymogen is expressed specifically in the pancreas and likely functions as a digestive enzyme.

Source: NCBI Gene 1506 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 58 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2524
Approved symbol	CTRL
Name	chymotrypsin like
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CTRL1
Ensembl gene	ENSG00000141086
Ensembl biotype	protein_coding
OMIM	118888
Entrez	1506

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000571044, ENST00000571605, ENST00000572144, ENST00000573845, ENST00000574481, ENST00000575302, ENST00000576408, ENST00000576915

RefSeq mRNA: 1 — MANE Select: NM_001907 NM_001907

CCDS: CCDS10852

Canonical transcript exons

ENST00000574481 — 7 exons

Exon	Start	End
ENSE00000946542	67931098	67931201
ENSE00001221145	67931801	67931862
ENSE00001329348	67929574	67930095
ENSE00003515563	67930920	67930999
ENSE00003569126	67930408	67930588
ENSE00003571438	67930185	67930318
ENSE00003617635	67930726	67930807

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.71.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.1071 / max 8733.8336, expressed in 8 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157828	5.0793	7
157827	0.0157	1
157826	0.0120	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.71	gold quality
pancreas	UBERON:0001264	94.91	gold quality
islet of Langerhans	UBERON:0000006	85.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.76	gold quality
granulocyte	CL:0000094	82.50	gold quality
blood	UBERON:0000178	81.33	gold quality
monocyte	CL:0000576	80.96	gold quality
leukocyte	CL:0000738	80.18	gold quality
bone marrow	UBERON:0002371	76.63	gold quality
spleen	UBERON:0002106	75.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.62	gold quality
bone marrow cell	CL:0002092	74.59	gold quality
cortical plate	UBERON:0005343	74.39	gold quality
cerebellum	UBERON:0002037	74.06	gold quality
cerebellar cortex	UBERON:0002129	74.03	gold quality
cerebellar hemisphere	UBERON:0002245	73.98	gold quality
ventricular zone	UBERON:0003053	73.53	gold quality
apex of heart	UBERON:0002098	73.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.02	gold quality
lymph node	UBERON:0000029	71.48	gold quality
colonic epithelium	UBERON:0000397	71.36	gold quality
putamen	UBERON:0001874	70.39	gold quality
primary visual cortex	UBERON:0002436	70.04	gold quality
adenohypophysis	UBERON:0002196	69.52	gold quality
mucosa of transverse colon	UBERON:0004991	69.24	gold quality
ovary	UBERON:0000992	69.22	gold quality
left ovary	UBERON:0002119	68.81	gold quality
upper lobe of left lung	UBERON:0008952	68.43	gold quality
vermiform appendix	UBERON:0001154	68.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	29.57
E-ANND-3	yes	24.29
E-MTAB-5061	yes	17.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting CTRL, 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-4534	99.99	66.58	1907
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-193A-5P	95.70	65.33	613
HSA-MIR-874-3P	95.02	65.66	806

Literature-anchored findings (GeneRIF, showing 1)

• We found CT-like activity to be an independent predictor of high-risk PCa, and as such, it may be a good candidate as a biomarker for high-risk PCa detection and stratification. (PMID:25578495)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctrl	ENSDARG00000068680
danio_rerio	si:dkey-238d18.3	ENSDARG00000088893
danio_rerio	zgc:171592	ENSDARG00000101964
mus_musculus	Ctrl	ENSMUSG00000031896
rattus_norvegicus	Psmb10	ENSRNOG00000019353

Paralogs (1): PRSS38 (ENSG00000185888)

Protein

Protein identifiers

Chymotrypsin-like protease CTRL-1 — P40313 (reviewed: P40313)

All UniProt accessions (3): P40313, I3L162, I3NI28

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_001898* (*=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 (15 total): disulfide bond 5, active site 3, sequence variant 2, signal peptide 1, propeptide 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40313-F1	91.26	0.79

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); 121 (charge relay system); 214 (charge relay system)

Disulfide bonds (5): 155–220, 187–201, 210–239, 19–141, 60–76

Glycosylation sites (1): 114

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells

MSigDB gene sets: 112 (showing top): MORF_FLT1, YAGI_AML_WITH_INV_16_TRANSLOCATION, chr16q22, MORF_MSH3, MORF_BRCA1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_ESR1, MORF_RAD51L3, BLALOCK_ALZHEIMERS_DISEASE_UP, KLEIN_PRIMARY_EFFUSION_LYMPHOMA_UP, MORF_PRKCA, MORF_ETV3, MORF_ATF2, SCHLOSSER_SERUM_RESPONSE_AUGMENTED_BY_MYC, MORF_BCL2L11

GO Biological Process (2): proteolysis (GO:0006508), protein catabolic process (GO:0030163)

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

GO Cellular Component (1): obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
macromolecule catabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1

Protein interactions and networks

STRING

2762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTRL	PSMB8	P28062	918
CTRL	PSMB10	P40306	861
CTRL	PSMB9	P28065	836
CTRL	PSMB5	P28074	832
CTRL	SERPINB4	P48594	781
CTRL	PSMB6	P28072	776
CTRL	PPP1CA	P08129	764
CTRL	ACE2	Q9BYF1	692
CTRL	GAPDH	P00354	637
CTRL	ACTB	P02570	630
CTRL	SERPINA3	P01011	607
CTRL	ALB	P02768	597
CTRL	SLC5A7	Q9GZV3	587
CTRL	CASP3	P42574	582
CTRL	APP	P05067	575

IntAct

16 interactions, top by confidence:

A	B	Type	Score
CTRL	FATE1	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	CTRL	psi-mi:“MI:0915”(physical association)	0.560
CTRL	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
CTRL	PSME1	psi-mi:“MI:0914”(association)	0.530
ING1	CTRL	psi-mi:“MI:0915”(physical association)	0.400
ASXL2	CTRL	psi-mi:“MI:0914”(association)	0.350
BCAN	LAMA5	psi-mi:“MI:0914”(association)	0.350
CTRL	SERPINA1	psi-mi:“MI:0914”(association)	0.350
CTRL	FATE1	psi-mi:“MI:0915”(physical association)	0.000
CTRL	FAM209A	psi-mi:“MI:0915”(physical association)	0.000
CTRL	CLDN5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): PDIA5 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME2 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), PSME2 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), CTRL (Two-hybrid), FATE1 (Two-hybrid), CLDN5 (Two-hybrid), CTRL (Affinity Capture-MS), PSME1 (Affinity Capture-MS), PSME2 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), CTRL (Affinity Capture-MS)

ESM2 similar proteins: A1KXI1, C0HKA2, C0HKA3, C0HKA4, C0HKA5, C0HKA6, C0HKF7, C0HKF8, O46644, O97370, P00760, P00765, P00766, P00772, P00773, P00774, P04814, P05208, P06871, P07477, P07478, P08217, P08218, P08426, P19799, P35003, P35004, P35005, P35031, P35033, P35043, P35044, P35049, P36178, P40313, P51588, P54624, P54625, P54627, P70059

Diamond homologs: A0A126GUP6, A0A182C2Z2, A0A1S4H5M5, A8JUP7, B5U2W0, B7YZU2, F5HKX0, O15393, O35453, O60235, O60259, O97366, P00774, P03951, P03952, P05049, P05981, P08419, P09871, P10323, P13582, P14272, P21902, P23578, P25155, P26262, P28175, P29293, P31394, P33587, P35035, P35036, P35037, P35039, P35041, P35045, P35046, P35047, P40313, P48038

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1237 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67930179:GCTTA:G	donor_loss	1.0000
16:67930180:CTTA:C	donor_loss	1.0000
16:67930181:TTA:T	donor_loss	1.0000
16:67930182:TACCT:T	donor_loss	1.0000
16:67930183:A:AC	donor_gain	1.0000
16:67930183:A:T	donor_loss	1.0000
16:67930184:C:CC	donor_gain	1.0000
16:67930315:TTGC:T	acceptor_gain	1.0000
16:67930316:TGC:T	acceptor_gain	1.0000
16:67930319:C:CA	acceptor_loss	1.0000
16:67930319:C:CC	acceptor_gain	1.0000
16:67930320:T:A	acceptor_loss	1.0000
16:67930403:CCTAC:C	donor_loss	1.0000
16:67930404:CTACC:C	donor_loss	1.0000
16:67930406:AC:A	donor_gain	1.0000
16:67930407:CC:C	donor_gain	1.0000
16:67930407:CCCA:C	donor_gain	1.0000
16:67930411:CGCCA:C	donor_gain	1.0000
16:67930584:ATGGC:A	acceptor_gain	1.0000
16:67930585:TGGC:T	acceptor_gain	1.0000
16:67930586:GGC:G	acceptor_gain	1.0000
16:67930587:GC:G	acceptor_gain	1.0000
16:67930588:CC:C	acceptor_gain	1.0000
16:67930589:C:CC	acceptor_gain	1.0000
16:67930590:T:G	acceptor_loss	1.0000
16:67930598:C:CT	acceptor_gain	1.0000
16:67930803:CAGGG:C	acceptor_gain	1.0000
16:67930808:C:CC	acceptor_gain	1.0000
16:67930915:CTCA:C	donor_loss	1.0000
16:67930916:TCAC:T	donor_loss	1.0000

AlphaMissense

1693 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67930427:C:A	W160C	0.999
16:67930427:C:G	W160C	0.999
16:67930091:T:A	D213V	0.997
16:67930545:T:A	D121V	0.997
16:67929961:C:A	W256C	0.996
16:67929961:C:G	W256C	0.996
16:67930216:C:G	C201S	0.996
16:67930217:A:T	C201S	0.996
16:67930545:T:G	D121A	0.996
16:67930546:C:G	D121H	0.996
16:67930929:C:G	C76S	0.996
16:67930929:C:T	C76Y	0.996
16:67930930:A:T	C76S	0.996
16:67930085:C:A	G215V	0.995
16:67930091:T:G	D213A	0.995
16:67930092:C:G	D213H	0.995
16:67930258:C:G	C187S	0.995
16:67930259:A:T	C187S	0.995
16:67930426:C:A	G161C	0.995
16:67930429:A:G	W160R	0.995
16:67930429:A:T	W160R	0.995
16:67930977:C:T	C60Y	0.995
16:67931115:A:G	W47R	0.995
16:67931115:A:T	W47R	0.995
16:67930189:C:G	C210S	0.994
16:67930190:A:T	C210S	0.994
16:67930215:A:C	C201W	0.994
16:67930216:C:T	C201Y	0.994
16:67930291:T:G	Q176P	0.994
16:67930432:C:A	G159C	0.994

dbSNP variants (sampled 300 via entrez): RS1000000135 (16:67933618 G>GTA), RS1001017670 (16:67929464 C>T), RS1001050531 (16:67929217 G>C), RS1002442769 (16:67929967 G>A), RS1002605621 (16:67931455 C>T), RS1003048026 (16:67932385 C>T), RS1003283536 (16:67932167 T>C), RS1004038722 (16:67931352 C>G,T), RS1004235988 (16:67930026 C>T), RS1004607429 (16:67930291 T>C), RS1005751013 (16:67929839 C>G), RS1007071887 (16:67929344 G>A,C), RS1007445519 (16:67933691 G>A), RS1008061642 (16:67933564 A>G), RS1009086628 (16:67932340 C>T)

Disease associations

OMIM: gene MIM:118888 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002539_84	Schizophrenia	2.000000e-08
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523987 (PROTEIN FAMILY), CHEMBL4873 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,872 (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
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL2103884	OPROZOMIB	2	2,738

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

ChEMBL bioactivities

63 potent at pChembl≥5 of 69 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
9.04	IC50	0.92	nM	CHEMBL5875469
9.01	IC50	0.97	nM	CHEMBL5777046
8.96	IC50	1.09	nM	CHEMBL5875469
8.87	IC50	1.34	nM	CHEMBL5777046
8.82	Ki	1.5	nM	CHEMBL4469390
8.70	IC50	2	nM	CHEMBL307387
8.45	IC50	3.58	nM	CHEMBL5762635
8.43	IC50	3.73	nM	CHEMBL5790408
8.37	IC50	4.26	nM	CHEMBL5790408
8.37	IC50	4.28	nM	CHEMBL5902905
8.33	IC50	4.65	nM	CHEMBL5762635
8.32	IC50	4.74	nM	CHEMBL5999781
8.29	IC50	5.1	nM	CHEMBL5999781
8.22	IC50	6	nM	CHEMBL74336
8.21	IC50	6.1	nM	CHEMBL5980630
8.18	IC50	6.56	nM	CHEMBL5753629
8.17	IC50	6.81	nM	CHEMBL5897043
8.13	IC50	7.41	nM	CHEMBL5902905
8.10	IC50	8	nM	CHEMBL98688
8.01	IC50	9.75	nM	CHEMBL6059829
7.96	Ki	11	nM	CHEMBL4590739
7.96	IC50	11.1	nM	CHEMBL5936824
7.91	IC50	12.2	nM	CHEMBL5897043
7.89	IC50	13	nM	CHEMBL317337
7.87	IC50	13.5	nM	CHEMBL5917064
7.85	IC50	14.2	nM	CHEMBL5936824
7.82	IC50	15.3	nM	CHEMBL6059829
7.80	IC50	16	nM	CHEMBL5970381
7.70	Ki	20	nM	CHEMBL4638245
7.66	IC50	22	nM	CHEMBL317337
7.55	IC50	28.1	nM	CHEMBL5753629
7.50	IC50	31.7	nM	CHEMBL5970381
7.48	IC50	33.3	nM	CHEMBL5852054
7.47	IC50	33.6	nM	CHEMBL5852054
7.46	Ki	35	nM	MILVEXIAN
7.23	IC50	59.3	nM	CHEMBL5980630
7.22	IC50	60.4	nM	CHEMBL5917064
7.21	IC50	62.4	nM	CHEMBL5778844
7.19	IC50	65	nM	CHEMBL1929019
7.01	IC50	98	nM	CHEMBL1929023
6.95	IC50	113	nM	CHEMBL6015382
6.92	IC50	121	nM	CHEMBL6011905
6.91	IC50	124	nM	OPROZOMIB
6.82	Ki	150	nM	CHEMBL4592765
6.77	IC50	170	nM	CHEMBL6011905
6.61	IC50	248	nM	CHEMBL5778844
6.59	IC50	256	nM	OPROZOMIB
6.57	IC50	270	nM	CHEMBL1929020

PubChem BioAssay actives

22 with measured affinity, of 152 total; 21 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-[(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
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
(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
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]propanoyl]amino]-N-[(2S)-3-cyclohexyl-1-[[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methylbutanamide	636874: Inhibition of chymotrypsin-like protease R188I mutant using peptide substrate SO1 measured after 60 mins by HPLC analysis	ic50	0.0650	uM
(2S)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-N-[(2S)-3-cyclohexyl-1-[[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methylbutanamide	636874: Inhibition of chymotrypsin-like protease R188I mutant using peptide substrate SO1 measured after 60 mins by HPLC analysis	ic50	0.0980	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
(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-N-[(2S)-3-cyclohexyl-1-[[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methylbutanamide	636874: Inhibition of chymotrypsin-like protease R188I mutant using peptide substrate SO1 measured after 60 mins by HPLC analysis	ic50	0.2700	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
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-N-[(2S)-3-cyclohexyl-1-[[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-methylbutanamide	636874: Inhibition of chymotrypsin-like protease R188I mutant using peptide substrate SO1 measured after 60 mins by HPLC analysis	ic50	0.3400	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
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]propanoyl]amino]-N-[(2S)-1-[[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-3-methylbutanamide	636874: Inhibition of chymotrypsin-like protease R188I mutant using peptide substrate SO1 measured after 60 mins by HPLC analysis	ic50	0.3900	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
[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
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
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-methylphenyl)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	1.5000	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-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	2.9000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-N-[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]-4-methylpentanamide	636874: Inhibition of chymotrypsin-like protease R188I mutant using peptide substrate SO1 measured after 60 mins by HPLC analysis	ic50	5.7000	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-3-cyclohexyl-1-[[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]butanediamide	636874: Inhibition of chymotrypsin-like protease R188I mutant using peptide substrate SO1 measured after 60 mins by HPLC analysis	ic50	10.0000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
uranyl acetate	affects expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
plumbagin	decreases activity, decreases reaction	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Acetylcysteine	decreases activity, decreases reaction	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Copper	affects binding, decreases expression	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1
Silicon Dioxide	increases expression	1
Tamoxifen	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Theophylline	increases expression	1
Uranium	affects expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Gold Compounds	increases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

61 unique, capped per target: 35 binding, 24 admet, 1 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)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea